<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2024 Workiva-->
<!--r:61b71ede-6647-4c77-a23a-5824606fce5b,g:5579ccb0-dcbb-4821-8f9d-2cb63b573045-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:vrtx="http://www.vrtx.com/20231231" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2022-03-31" xmlns:dtr-types1="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.vrtx.com/20231231">
  <xs:import namespace="http://fasb.org/srt/2023" schemaLocation="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2023" schemaLocation="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd"/>
  <xs:import namespace="http://www.w3.org/1999/xlink" schemaLocation="http://www.xbrl.org/2003/xlink-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2022-03-31" schemaLocation="https://www.xbrl.org/dtr/type/2022-03-31/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/country/2023" schemaLocation="https://xbrl.sec.gov/country/2023/country-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/currency/2023" schemaLocation="https://xbrl.sec.gov/currency/2023/currency-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2023" schemaLocation="https://xbrl.sec.gov/dei/2023/dei-2023.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd/2023" schemaLocation="https://xbrl.sec.gov/ecd/2023/ecd-2023.xsd"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="vrtx-20231231_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="vrtx-20231231_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="vrtx-20231231_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="vrtx-20231231_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="Cover" roleURI="http://www.vrtx.com/role/Cover">
        <link:definition>0000001 - Document - Cover</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AuditInformation" roleURI="http://www.vrtx.com/role/AuditInformation">
        <link:definition>0000002 - Document - Audit Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofIncome" roleURI="http://www.vrtx.com/role/ConsolidatedStatementsofIncome">
        <link:definition>0000003 - Statement - Consolidated Statements of Income</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofComprehensiveIncome" roleURI="http://www.vrtx.com/role/ConsolidatedStatementsofComprehensiveIncome">
        <link:definition>0000004 - Statement - Consolidated Statements of Comprehensive Income</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofComprehensiveIncomeParenthetical" roleURI="http://www.vrtx.com/role/ConsolidatedStatementsofComprehensiveIncomeParenthetical">
        <link:definition>0000005 - Statement - Consolidated Statements of Comprehensive Income (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedBalanceSheets" roleURI="http://www.vrtx.com/role/ConsolidatedBalanceSheets">
        <link:definition>0000006 - Statement - Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedBalanceSheetsParenthetical" roleURI="http://www.vrtx.com/role/ConsolidatedBalanceSheetsParenthetical">
        <link:definition>0000007 - Statement - Consolidated Balance Sheets (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofShareholdersEquity" roleURI="http://www.vrtx.com/role/ConsolidatedStatementsofShareholdersEquity">
        <link:definition>0000008 - Statement - Consolidated Statements of Shareholders&#8217; Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofCashFlows" roleURI="http://www.vrtx.com/role/ConsolidatedStatementsofCashFlows">
        <link:definition>0000009 - Statement - Consolidated Statements of Cash Flows</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPolicies" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPolicies">
        <link:definition>0000010 - Disclosure - Nature of Business and Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationLicenseandOtherArrangements" roleURI="http://www.vrtx.com/role/CollaborationLicenseandOtherArrangements">
        <link:definition>0000011 - Disclosure - Collaboration, License and Other Arrangements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="EarningsPerShare" roleURI="http://www.vrtx.com/role/EarningsPerShare">
        <link:definition>0000012 - Disclosure - Earnings Per Share</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurements" roleURI="http://www.vrtx.com/role/FairValueMeasurements">
        <link:definition>0000013 - Disclosure - Fair Value Measurements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestments" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestments">
        <link:definition>0000014 - Disclosure - Marketable Securities and Equity Investments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccumulatedOtherComprehensiveIncomeLoss" roleURI="http://www.vrtx.com/role/AccumulatedOtherComprehensiveIncomeLoss">
        <link:definition>0000015 - Disclosure - Accumulated Other Comprehensive Income (Loss)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Hedging" roleURI="http://www.vrtx.com/role/Hedging">
        <link:definition>0000016 - Disclosure - Hedging</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Inventories" roleURI="http://www.vrtx.com/role/Inventories">
        <link:definition>0000017 - Disclosure - Inventories</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipment" roleURI="http://www.vrtx.com/role/PropertyandEquipment">
        <link:definition>0000018 - Disclosure - Property and Equipment</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="GoodwillandOtherIntangibleAssets" roleURI="http://www.vrtx.com/role/GoodwillandOtherIntangibleAssets">
        <link:definition>0000019 - Disclosure - Goodwill and Other Intangible Assets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetail" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetail">
        <link:definition>0000020 - Disclosure - Additional Balance Sheet Detail</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Leases" roleURI="http://www.vrtx.com/role/Leases">
        <link:definition>0000021 - Disclosure - Leases</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlans" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlans">
        <link:definition>0000022 - Disclosure - Common Stock, Preferred Stock and Equity Plans</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationExpense" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpense">
        <link:definition>0000023 - Disclosure - Stock-based Compensation Expense</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxes" roleURI="http://www.vrtx.com/role/IncomeTaxes">
        <link:definition>0000024 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingencies" roleURI="http://www.vrtx.com/role/CommitmentsandContingencies">
        <link:definition>0000025 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentInformation" roleURI="http://www.vrtx.com/role/SegmentInformation">
        <link:definition>0000026 - Disclosure - Segment Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesPolicies" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesPolicies">
        <link:definition>9954471 - Disclosure - Nature of Business and Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesTables" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesTables">
        <link:definition>9954472 - Disclosure - Nature of Business and Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="EarningsPerShareTables" roleURI="http://www.vrtx.com/role/EarningsPerShareTables">
        <link:definition>9954473 - Disclosure - Earnings Per Share (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsTables" roleURI="http://www.vrtx.com/role/FairValueMeasurementsTables">
        <link:definition>9954474 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsTables" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsTables">
        <link:definition>9954475 - Disclosure - Marketable Securities and Equity Investments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccumulatedOtherComprehensiveIncomeLossTables" roleURI="http://www.vrtx.com/role/AccumulatedOtherComprehensiveIncomeLossTables">
        <link:definition>9954476 - Disclosure - Accumulated Other Comprehensive Income (Loss) (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="HedgingTables" roleURI="http://www.vrtx.com/role/HedgingTables">
        <link:definition>9954477 - Disclosure - Hedging (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="InventoriesTables" roleURI="http://www.vrtx.com/role/InventoriesTables">
        <link:definition>9954478 - Disclosure - Inventories (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipmentTables" roleURI="http://www.vrtx.com/role/PropertyandEquipmentTables">
        <link:definition>9954479 - Disclosure - Property and Equipment (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="GoodwillandOtherIntangibleAssetsTables" roleURI="http://www.vrtx.com/role/GoodwillandOtherIntangibleAssetsTables">
        <link:definition>9954480 - Disclosure - Goodwill and Other Intangible Assets (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetailTables" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailTables">
        <link:definition>9954481 - Disclosure - Additional Balance Sheet Detail (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesTables" roleURI="http://www.vrtx.com/role/LeasesTables">
        <link:definition>9954482 - Disclosure - Leases (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansTables" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansTables">
        <link:definition>9954483 - Disclosure - Common Stock, Preferred Stock and Equity Plans (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationExpenseTables" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseTables">
        <link:definition>9954484 - Disclosure - Stock-based Compensation Expense (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesTables" roleURI="http://www.vrtx.com/role/IncomeTaxesTables">
        <link:definition>9954485 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentInformationTables" roleURI="http://www.vrtx.com/role/SegmentInformationTables">
        <link:definition>9954486 - Disclosure - Segment Information (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesBusinessDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesBusinessDetails">
        <link:definition>9954487 - Disclosure - Nature of Business and Accounting Policies - Business (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesBasisofPresentationDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesBasisofPresentationDetails">
        <link:definition>9954488 - Disclosure - Nature of Business and Accounting Policies - Basis of Presentation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesRevenueRecognitionDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesRevenueRecognitionDetails">
        <link:definition>9954489 - Disclosure - Nature of Business and Accounting Policies - Revenue Recognition (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesStockBasedCompensationExpenseDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesStockBasedCompensationExpenseDetails">
        <link:definition>9954490 - Disclosure - Nature of Business and Accounting Policies - Stock-Based Compensation Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesscheduleofPropertyandEquipmentDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesscheduleofPropertyandEquipmentDetails">
        <link:definition>9954491 - Disclosure - Nature of Business and Accounting Policies - schedule of Property and Equipment (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessandAccountingPoliciesGoodwillHedgingActivitiesForeignCurrencyGainLossDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesGoodwillHedgingActivitiesForeignCurrencyGainLossDetails">
        <link:definition>9954492 - Disclosure - Nature of Business and Accounting Policies - Goodwill Hedging Activities Foreign Currency Gain (Loss) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CollaborationLicenseandOtherArrangementsDetails" roleURI="http://www.vrtx.com/role/CollaborationLicenseandOtherArrangementsDetails">
        <link:definition>9954493 - Disclosure - Collaboration, License and Other Arrangements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="EarningsPerShareScheduleofComputationDetails" roleURI="http://www.vrtx.com/role/EarningsPerShareScheduleofComputationDetails">
        <link:definition>9954494 - Disclosure - Earnings Per Share - Schedule of Computation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="EarningsPerShareScheduleofAntidilutiveSecuritiesDetails" roleURI="http://www.vrtx.com/role/EarningsPerShareScheduleofAntidilutiveSecuritiesDetails">
        <link:definition>9954495 - Disclosure - Earnings Per Share - Schedule of Anti-dilutive Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/FairValueMeasurementsAdditionalInformationDetails">
        <link:definition>9954496 - Disclosure - Fair Value Measurements - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsScheduleofFinancialAssetsandLiabilitiesSubjecttoFairValueMeasurementsDetails" roleURI="http://www.vrtx.com/role/FairValueMeasurementsScheduleofFinancialAssetsandLiabilitiesSubjecttoFairValueMeasurementsDetails">
        <link:definition>9954497 - Disclosure - Fair Value Measurements - Schedule of Financial Assets and Liabilities Subject to Fair Value Measurements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueMeasurementsScheduleofFairValueofContingentConsiderationLiabilitiesDetails" roleURI="http://www.vrtx.com/role/FairValueMeasurementsScheduleofFairValueofContingentConsiderationLiabilitiesDetails">
        <link:definition>9954498 - Disclosure - Fair Value Measurements - Schedule of Fair Value of Contingent Consideration Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsAdditionalInformationDetails">
        <link:definition>9954499 - Disclosure - Marketable Securities and Equity Investments - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsScheduleofCashEquivalentsandMarketableSecuritiesDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsScheduleofCashEquivalentsandMarketableSecuritiesDetails">
        <link:definition>9954500 - Disclosure - Marketable Securities and Equity Investments - Schedule of Cash Equivalents and Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsScheduleofCashEquivalentsandMarketableSecuritiesDetails_1" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsScheduleofCashEquivalentsandMarketableSecuritiesDetails_1">
        <link:definition>9954500 - Disclosure - Marketable Securities and Equity Investments - Schedule of Cash Equivalents and Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsScheduleofAvailableforSaleDebtSecuritiesatFairValueDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsScheduleofAvailableforSaleDebtSecuritiesatFairValueDetails">
        <link:definition>9954501 - Disclosure - Marketable Securities and Equity Investments - Schedule of Available-for-Sale Debt Securities at Fair Value (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsscheduleofAvailableforSaleDebtSecuritiesbyContractualMaturityDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsscheduleofAvailableforSaleDebtSecuritiesbyContractualMaturityDetails">
        <link:definition>9954502 - Disclosure - Marketable Securities and Equity Investments - schedule of Available-for-Sale Debt Securities by Contractual Maturity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesandEquityInvestmentsNetUnrealizedGainsLossesDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsNetUnrealizedGainsLossesDetails">
        <link:definition>9954503 - Disclosure - Marketable Securities and Equity Investments - Net Unrealized Gains (Losses) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccumulatedOtherComprehensiveIncomeLossDetails" roleURI="http://www.vrtx.com/role/AccumulatedOtherComprehensiveIncomeLossDetails">
        <link:definition>9954504 - Disclosure - Accumulated Other Comprehensive Income (Loss) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="HedgingAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/HedgingAdditionalInformationDetails">
        <link:definition>9954505 - Disclosure - Hedging - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="HedgingScheduleofNotionalAmountDetails" roleURI="http://www.vrtx.com/role/HedgingScheduleofNotionalAmountDetails">
        <link:definition>9954506 - Disclosure - Hedging - Schedule of Notional Amount (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="HedgingScheduleofCashFlowHedgingInstrumentsDetails" roleURI="http://www.vrtx.com/role/HedgingScheduleofCashFlowHedgingInstrumentsDetails">
        <link:definition>9954507 - Disclosure - Hedging - Schedule of Cash Flow Hedging Instruments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="HedgingScheduleofDerivativeFairValueDetails" roleURI="http://www.vrtx.com/role/HedgingScheduleofDerivativeFairValueDetails">
        <link:definition>9954508 - Disclosure - Hedging - Schedule of Derivative Fair Value (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="HedgingScheduleofOffsettingDerivativesDetails" roleURI="http://www.vrtx.com/role/HedgingScheduleofOffsettingDerivativesDetails">
        <link:definition>9954509 - Disclosure - Hedging - Schedule of Offsetting Derivatives (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="InventoriesDetails" roleURI="http://www.vrtx.com/role/InventoriesDetails">
        <link:definition>9954510 - Disclosure - Inventories (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipmentScheduleofPropertyandEquipmentNetDetails" roleURI="http://www.vrtx.com/role/PropertyandEquipmentScheduleofPropertyandEquipmentNetDetails">
        <link:definition>9954511 - Disclosure - Property and Equipment - Schedule of Property and Equipment, Net (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipmentAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/PropertyandEquipmentAdditionalInformationDetails">
        <link:definition>9954512 - Disclosure - Property and Equipment - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="GoodwillandOtherIntangibleAssetsScheduleofIntangibleAssetsandGoodwillDetails" roleURI="http://www.vrtx.com/role/GoodwillandOtherIntangibleAssetsScheduleofIntangibleAssetsandGoodwillDetails">
        <link:definition>9954513 - Disclosure - Goodwill and Other Intangible Assets - Schedule of Intangible Assets and Goodwill (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="GoodwillandOtherIntangibleAssetsScheduleofIntangibleAssetsandGoodwillDetails_1" roleURI="http://www.vrtx.com/role/GoodwillandOtherIntangibleAssetsScheduleofIntangibleAssetsandGoodwillDetails_1">
        <link:definition>9954513 - Disclosure - Goodwill and Other Intangible Assets - Schedule of Intangible Assets and Goodwill (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="GoodwillandOtherIntangibleAssetsAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/GoodwillandOtherIntangibleAssetsAdditionalInformationDetails">
        <link:definition>9954514 - Disclosure - Goodwill and Other Intangible Assets - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="GoodwillandOtherIntangibleAssetsScheduleofFutureAmortizationExpenseDetails" roleURI="http://www.vrtx.com/role/GoodwillandOtherIntangibleAssetsScheduleofFutureAmortizationExpenseDetails">
        <link:definition>9954515 - Disclosure - Goodwill and Other Intangible Assets - Schedule of Future Amortization Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetailScheduleofPrepaidExpensesandOtherCurrentAssetsDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailScheduleofPrepaidExpensesandOtherCurrentAssetsDetails">
        <link:definition>9954516 - Disclosure - Additional Balance Sheet Detail - Schedule of Prepaid Expenses and Other Current Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetailScheduleofAccruedExpensesandOtherCurrentLiabilitiesDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailScheduleofAccruedExpensesandOtherCurrentLiabilitiesDetails">
        <link:definition>9954517 - Disclosure - Additional Balance Sheet Detail - Schedule of Accrued Expenses and Other Current Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetailScheduleofOtherLongTermLiabilitiesDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailScheduleofOtherLongTermLiabilitiesDetails">
        <link:definition>9954518 - Disclosure - Additional Balance Sheet Detail - Schedule of Other Long Term Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetailScheduleofAdditionalCashFlowDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailScheduleofAdditionalCashFlowDetails">
        <link:definition>9954519 - Disclosure - Additional Balance Sheet Detail - Schedule of Additional Cash Flow (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AdditionalBalanceSheetDetailAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailAdditionalInformationDetails">
        <link:definition>9954520 - Disclosure - Additional Balance Sheet Detail - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/LeasesAdditionalInformationDetails">
        <link:definition>9954521 - Disclosure - Leases - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofComponentsofLeaseExpenseDetails" roleURI="http://www.vrtx.com/role/LeasesScheduleofComponentsofLeaseExpenseDetails">
        <link:definition>9954522 - Disclosure - Leases - Schedule of Components of Lease Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofBalanceSheetClassificationofLeaseAssetsandLiabilitiesDetails" roleURI="http://www.vrtx.com/role/LeasesScheduleofBalanceSheetClassificationofLeaseAssetsandLiabilitiesDetails">
        <link:definition>9954523 - Disclosure - Leases - Schedule of Balance Sheet Classification of Lease Assets and Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails" roleURI="http://www.vrtx.com/role/LeasesScheduleofMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails">
        <link:definition>9954524 - Disclosure - Leases -Schedule of Maturities of Operating and Financing Lease Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_1" roleURI="http://www.vrtx.com/role/LeasesScheduleofMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_1">
        <link:definition>9954524 - Disclosure - Leases -Schedule of Maturities of Operating and Financing Lease Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_2" roleURI="http://www.vrtx.com/role/LeasesScheduleofMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_2">
        <link:definition>9954524 - Disclosure - Leases -Schedule of Maturities of Operating and Financing Lease Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofWeightedAverageRemainingLeaseTermsandDiscountRatesDetails" roleURI="http://www.vrtx.com/role/LeasesScheduleofWeightedAverageRemainingLeaseTermsandDiscountRatesDetails">
        <link:definition>9954525 - Disclosure - Leases - Schedule of Weighted-Average Remaining Lease Terms and Discount Rates (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LeasesScheduleofSupplementalCashFlowInformationDetails" roleURI="http://www.vrtx.com/role/LeasesScheduleofSupplementalCashFlowInformationDetails">
        <link:definition>9954526 - Disclosure - Leases - Schedule of Supplemental Cash Flow Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansCommonStockandPreferredStockDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansCommonStockandPreferredStockDetails">
        <link:definition>9954527 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Common Stock and Preferred Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansShareRepurchaseProgramDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansShareRepurchaseProgramDetails">
        <link:definition>9954528 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Share Repurchase Program (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansStockandOptionPlansDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansStockandOptionPlansDetails">
        <link:definition>9954529 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Stock and Option Plans (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansRestrictedStockandRestrictedStockUnitsDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansRestrictedStockandRestrictedStockUnitsDetails">
        <link:definition>9954530 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Restricted Stock and Restricted Stock Units (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansPerformancebasedRSUsPSUsDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansPerformancebasedRSUsPSUsDetails">
        <link:definition>9954531 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Performance-based RSUs (PSUs) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansOutstandingandExercisableOptionsDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansOutstandingandExercisableOptionsDetails">
        <link:definition>9954532 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Outstanding and Exercisable Options (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansStockOptionsOutstandingandExercisableDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansStockOptionsOutstandingandExercisableDetails">
        <link:definition>9954533 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Stock Options Outstanding and Exercisable (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansEmployeeStockPurchasePlanDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansEmployeeStockPurchasePlanDetails">
        <link:definition>9954534 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Employee Stock Purchase Plan (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockPreferredStockandEquityPlansEmployeeBenefitsDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansEmployeeBenefitsDetails">
        <link:definition>9954535 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Employee Benefits (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationExpenseScheduleofStockbasedCompensationExpensebyLineItemDetails" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseScheduleofStockbasedCompensationExpensebyLineItemDetails">
        <link:definition>9954536 - Disclosure - Stock-based Compensation Expense - Schedule of Stock-based Compensation Expense by Line Item (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationExpenseAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseAdditionalInformationDetails">
        <link:definition>9954537 - Disclosure - Stock-based Compensation Expense - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationExpenseScheduleofUnrecognizedStockBasedCompensationExpenseDetails" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseScheduleofUnrecognizedStockBasedCompensationExpenseDetails">
        <link:definition>9954538 - Disclosure - Stock-based Compensation Expense - Schedule of Unrecognized Stock-Based Compensation Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockbasedCompensationExpenseScheduleofweightedaverageAssumptionsDetails" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseScheduleofweightedaverageAssumptionsDetails">
        <link:definition>9954539 - Disclosure - Stock-based Compensation Expense - Schedule of weighted-average Assumptions (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesScheduleofComponentsofIncomeandProvisionforBenefitfromIncomeTaxesDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesScheduleofComponentsofIncomeandProvisionforBenefitfromIncomeTaxesDetails">
        <link:definition>9954540 - Disclosure - Income Taxes - Schedule of Components of Income and Provision for (Benefit from) Income Taxes (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesScheduleofEffectiveIncomeTaxReconciliationDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesScheduleofEffectiveIncomeTaxReconciliationDetails">
        <link:definition>9954541 - Disclosure - Income Taxes - Schedule of Effective Income Tax Reconciliation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesAdditionalInformationDetails">
        <link:definition>9954542 - Disclosure - Income Taxes - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesScheduleofDeferredTaxAssetsandLiabilitiesDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesScheduleofDeferredTaxAssetsandLiabilitiesDetails">
        <link:definition>9954543 - Disclosure - Income Taxes - Schedule of Deferred Tax Assets and Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesUnrecognizedTaxBenefitsDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesUnrecognizedTaxBenefitsDetails">
        <link:definition>9954544 - Disclosure - Income Taxes - Unrecognized Tax Benefits (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesDetails" roleURI="http://www.vrtx.com/role/CommitmentsandContingenciesDetails">
        <link:definition>9954545 - Disclosure - Commitments and Contingencies (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentInformationScheduleofRevenuesbyProductDetails" roleURI="http://www.vrtx.com/role/SegmentInformationScheduleofRevenuesbyProductDetails">
        <link:definition>9954546 - Disclosure - Segment Information - Schedule of Revenues by Product (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentInformationScheduleofRevenuebyGeographicLocationDetails" roleURI="http://www.vrtx.com/role/SegmentInformationScheduleofRevenuebyGeographicLocationDetails">
        <link:definition>9954547 - Disclosure - Segment Information - Schedule of Revenue by Geographic Location (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentInformationScheduleofSignificantCustomersDetails" roleURI="http://www.vrtx.com/role/SegmentInformationScheduleofSignificantCustomersDetails">
        <link:definition>9954548 - Disclosure - Segment Information - Schedule of Significant Customers (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentInformationScheduleofPropertyandEquipmentNetbyLocationDetails" roleURI="http://www.vrtx.com/role/SegmentInformationScheduleofPropertyandEquipmentNetbyLocationDetails">
        <link:definition>9954549 - Disclosure - Segment Information - Schedule of Property and Equipment, Net by Location (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:element id="vrtx_DebtCovenantConsolidatedLeverageRatio" abstract="false" name="DebtCovenantConsolidatedLeverageRatio" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="vrtx_CRISPRT1DMember" abstract="true" name="CRISPRT1DMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars20001ToDollars34273Member" abstract="true" name="ExercisePriceRangeFromDollars20001ToDollars34273Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_LesseeLeasingArrangementsCapitalLeasesRenewalTerm" abstract="false" name="LesseeLeasingArrangementsCapitalLeasesRenewalTerm" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_NonFinancialPerformanceSharesMember" abstract="true" name="NonFinancialPerformanceSharesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_TaxCarryforwardsLineItems" abstract="true" name="TaxCarryforwardsLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_InProcessResearchAndDevelopmentAssetsAndContingentPaymentsPolicyTextBlock" abstract="false" name="InProcessResearchAndDevelopmentAssetsAndContingentPaymentsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_LeaseAgreementNumberOfLeases" abstract="false" name="LeaseAgreementNumberOfLeases" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_FinanceLeasandOperatingLeaseLiabilitiesPaymentsDueAbstract" abstract="true" name="FinanceLeasandOperatingLeaseLiabilitiesPaymentsDueAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementsByAgreementDomain" abstract="true" name="CollaborativeArrangementsByAgreementDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_OtherContractLiabilitiesCurrent" abstract="false" name="OtherContractLiabilitiesCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_LicenseAgreementUpfrontPaymentReimbursement" abstract="false" name="LicenseAgreementUpfrontPaymentReimbursement" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_SYMDEKOSYMKEVIMember" abstract="true" name="SYMDEKOSYMKEVIMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_FinancialPerformanceSharesMember" abstract="true" name="FinancialPerformanceSharesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_WeightedAverageRemainingContractualLifeAbstract" abstract="true" name="WeightedAverageRemainingContractualLifeAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ApolLo1BioLLCMember" abstract="true" name="ApolLo1BioLLCMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_LicenseAgreementContingencyPayment" abstract="false" name="LicenseAgreementContingencyPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMinimum" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMinimum" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_LaboratoryEquipmentOtherEquipmentAndFurnitureMember" abstract="true" name="LaboratoryEquipmentOtherEquipmentAndFurnitureMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_TaxRelatedLiabilitiesNoncurrent" abstract="false" name="TaxRelatedLiabilitiesNoncurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_SecuredOvernightFinancingRateSOFRMember" abstract="true" name="SecuredOvernightFinancingRateSOFRMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_OutsidetheUnitedStatesMember" abstract="true" name="OutsidetheUnitedStatesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ProceedsFromFinanceLeasesAndOtherFinancingActivities" abstract="false" name="ProceedsFromFinanceLeasesAndOtherFinancingActivities" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueYearFour" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueYearFour" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueYearFive" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueYearFive" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentsDue" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentsDue" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_IndemnificationClaims" abstract="false" name="IndemnificationClaims" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_AccredoHealthGroupIncMember" abstract="true" name="AccredoHealthGroupIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_LeaseSupplementalCashFlowInformationTableTextBlock" abstract="false" name="LeaseSupplementalCashFlowInformationTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_BusinessCombinationRemainingMilestonePayment" abstract="false" name="BusinessCombinationRemainingMilestonePayment" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementUpFrontLicenseFee" abstract="false" name="CollaborativeArrangementUpFrontLicenseFee" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationbyShareBasedPaymentAwardPerformancePeriod" abstract="false" name="ShareBasedCompensationbyShareBasedPaymentAwardPerformancePeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementAllocationOfNetProfitsAndLossesPercent" abstract="false" name="CollaborativeArrangementAllocationOfNetProfitsAndLossesPercent" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars10001ToDollars15000Member" abstract="true" name="ExercisePriceRangeFromDollars10001ToDollars15000Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_CashEquivalentsAndDebtSecuritiesAvailableForSale" abstract="false" name="CashEquivalentsAndDebtSecuritiesAvailableForSale" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ScheduleofWeightedAverageRemainingLeaseTermsandDiscountRatesRelatedtoLeasesTableTextBlock" abstract="false" name="ScheduleofWeightedAverageRemainingLeaseTermsandDiscountRatesRelatedtoLeasesTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityUndiscountedExcessAmount" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityUndiscountedExcessAmount" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_WeightedAverageRemainingLeaseAbstract" abstract="true" name="WeightedAverageRemainingLeaseAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_DebtandEquitySecuritiesUnrealizedGain" abstract="false" name="DebtandEquitySecuritiesUnrealizedGain" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_SharebasedCompensationArrangementbySharebasedPaymentAwardDurationofPurchasePeriod" abstract="false" name="SharebasedCompensationArrangementbySharebasedPaymentAwardDurationofPurchasePeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_ArborBiotechnologiesIncMember" abstract="true" name="ArborBiotechnologiesIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ProductSalesAccruedLiabilities" abstract="false" name="ProductSalesAccruedLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementReimbursementOfContingencyPaymentPercent" abstract="false" name="CollaborativeArrangementReimbursementOfContingencyPaymentPercent" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="vrtx_ScheduleofUnrecognizedSharebasedCompensationExpenseTableTextBlock" abstract="false" name="ScheduleofUnrecognizedSharebasedCompensationExpenseTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementMilestoneAndUpfrontPayment" abstract="false" name="CollaborativeArrangementMilestoneAndUpfrontPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CRISPRMember" abstract="true" name="CRISPRMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_Percentageofemployeeseligibleforaccelerationofequityawards" abstract="false" name="Percentageofemployeeseligibleforaccelerationofequityawards" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_JeffreyLeidenCenterForCellAndGeneticTherapiesMember" abstract="true" name="JeffreyLeidenCenterForCellAndGeneticTherapiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_EffectiveIncomeTaxRateReconciliationUncertainTaxPositionsPercent" abstract="false" name="EffectiveIncomeTaxRateReconciliationUncertainTaxPositionsPercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_PubliclyTradedCompaniesSaleMember" abstract="true" name="PubliclyTradedCompaniesSaleMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueAfterYearFive" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueAfterYearFive" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_KalydecoMember" abstract="true" name="KalydecoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOutstandingNumber" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOutstandingNumber" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="vrtx_LineOfCreditFacilityAdditionalBorrowingCapacity" abstract="false" name="LineOfCreditFacilityAdditionalBorrowingCapacity" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_UnrecognizedTaxBenefitsIncreaseDecreaseInDeferredTaxAssetsGross" abstract="false" name="UnrecognizedTaxBenefitsIncreaseDecreaseInDeferredTaxAssetsGross" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentDueYearTwo" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentDueYearTwo" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_WalgreenCo.Member" abstract="true" name="WalgreenCo.Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ContingentLiabilities" abstract="false" name="ContingentLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_WeightedAverageDiscountRateAbstract" abstract="true" name="WeightedAverageDiscountRateAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_AssetsAndLiabilitiesLesseeTableTextBlock" abstract="false" name="AssetsAndLiabilitiesLesseeTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementAllocationOfResearchAndDevelopmentExpensesPercent" abstract="false" name="CollaborativeArrangementAllocationOfResearchAndDevelopmentExpensesPercent" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_EntradaTherapeuticsMember" abstract="true" name="EntradaTherapeuticsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_DebtCovenantIncreaseInConsolidatedLeverageRatio" abstract="false" name="DebtCovenantIncreaseInConsolidatedLeverageRatio" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementsByAgreementAxis" abstract="true" name="CollaborativeArrangementsByAgreementAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_LesseeLeasingArrangementsCapitalLeasesTermofContract" abstract="false" name="LesseeLeasingArrangementsCapitalLeasesTermofContract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_EditasMedicineIncMember" abstract="true" name="EditasMedicineIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_FanPierLeasesMember" abstract="true" name="FanPierLeasesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_LeaseAgreementNumberOfBuildings" abstract="false" name="LeaseAgreementNumberOfBuildings" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesTable" abstract="true" name="ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ORKAMBIMember" abstract="true" name="ORKAMBIMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_DeferredTaxAssetsOperatingLeaseAssets" abstract="false" name="DeferredTaxAssetsOperatingLeaseAssets" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_SharebasedCompensationArrangementbySharebasedPaymentAwardNumberofPurchasePeriods" abstract="false" name="SharebasedCompensationArrangementbySharebasedPaymentAwardNumberofPurchasePeriods" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_AggregateIntrinsicValueAbstract" abstract="true" name="AggregateIntrinsicValueAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_SepternaIncMember" abstract="true" name="SepternaIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CashEquivalentsAndDebtSecuritiesAvailableForSaleFairValueDisclosure" abstract="false" name="CashEquivalentsAndDebtSecuritiesAvailableForSaleFairValueDisclosure" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_NonemployeeStockOptionMember" abstract="true" name="NonemployeeStockOptionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_DeferredTaxAssetsMember" abstract="true" name="DeferredTaxAssetsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_LicenseAgreementUpfrontPaymentNet" abstract="false" name="LicenseAgreementUpfrontPaymentNet" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodFairValue" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodFairValue" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_DeferredTaxAssetsLeaseObligation" abstract="false" name="DeferredTaxAssetsLeaseObligation" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_NoncashFinancingOrInvestingActivitiesCollaborativeArrangementMilestonePaymentsDue" abstract="false" name="NoncashFinancingOrInvestingActivitiesCollaborativeArrangementMilestonePaymentsDue" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_NumberOfApprovedCysticFibrosisMedicines" abstract="false" name="NumberOfApprovedCysticFibrosisMedicines" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_RightOfUseAssetObtainedInExchangeForLeaseLiabilityAbstract" abstract="true" name="RightOfUseAssetObtainedInExchangeForLeaseLiabilityAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementRightToLicenseNumberOfTargets" abstract="false" name="CollaborativeArrangementRightToLicenseNumberOfTargets" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationTableTextBlock" abstract="false" name="IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_DeferredTaxAssetsIntangibles" abstract="false" name="DeferredTaxAssetsIntangibles" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars15001ToDollars20000Member" abstract="true" name="ExercisePriceRangeFromDollars15001ToDollars20000Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationAllocationAbstract" abstract="true" name="ShareBasedCompensationAllocationAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_DebtandEquitySecuritiesFairValue" abstract="false" name="DebtandEquitySecuritiesFairValue" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_UnrecognizedTaxBenefitsDeferredTaxLiabilitiesGross" abstract="false" name="UnrecognizedTaxBenefitsDeferredTaxLiabilitiesGross" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_TRIKAFTAKAFTRIOMember" abstract="true" name="TRIKAFTAKAFTRIOMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_StockandOptionPlan2013Member" abstract="true" name="StockandOptionPlan2013Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMaximum" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMaximum" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_ModernaAgreementMember" abstract="true" name="ModernaAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ShareRepurchaseProgram2020Member" abstract="true" name="ShareRepurchaseProgram2020Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_McKessonCorporationMember" abstract="true" name="McKessonCorporationMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_MarketableSecuritiesMember" abstract="true" name="MarketableSecuritiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentDueNextTwelveMonths" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentDueNextTwelveMonths" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_OtherCountriesOutsideoftheUnitedStatesandEuropeMember" abstract="true" name="OtherCountriesOutsideoftheUnitedStatesandEuropeMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_LesseeOperatingLeaseNumberOfRenewalOptions" abstract="false" name="LesseeOperatingLeaseNumberOfRenewalOptions" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_MarketableSecuritiesNoncurrentMember" abstract="true" name="MarketableSecuritiesNoncurrentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_SharebasedCompensationArrangementbySharebasedPaymentAwardOfferingPeriod" abstract="false" name="SharebasedCompensationArrangementbySharebasedPaymentAwardOfferingPeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_DebtandEquitySecuritiesCost" abstract="false" name="DebtandEquitySecuritiesCost" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_MarketableSecuritiesAndOtherNoncurrentAssetsMember" abstract="true" name="MarketableSecuritiesAndOtherNoncurrentAssetsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityPaymentDueYearThree" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentDueYearThree" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CRISPRTherapeuticsAGMember" abstract="true" name="CRISPRTherapeuticsAGMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_PaymentToAcquireCommonStock" abstract="false" name="PaymentToAcquireCommonStock" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars7731ToDollars10000Member" abstract="true" name="ExercisePriceRangeFromDollars7731ToDollars10000Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ScheduleOfStockAndStockOptionEquityPlansTableTextBlock" abstract="false" name="ScheduleOfStockAndStockOptionEquityPlansTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementReimbursementOfUpfrontPaymentPercent" abstract="false" name="CollaborativeArrangementReimbursementOfUpfrontPaymentPercent" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="vrtx_TaxRelatedPrepaidAndReceivables" abstract="false" name="TaxRelatedPrepaidAndReceivables" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesLineItems" abstract="true" name="ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_VerveMember" abstract="true" name="VerveMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_AccruedResearchDevelopmentAndCommercialContractCosts" abstract="false" name="AccruedResearchDevelopmentAndCommercialContractCosts" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CRISPRARJDCAMember" abstract="true" name="CRISPRARJDCAMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_StockAndOptionPlan2006Member" abstract="true" name="StockAndOptionPlan2006Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfInstallments" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfInstallments" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_CommonStockVotesPerEachShare" abstract="false" name="CommonStockVotesPerEachShare" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiability" abstract="false" name="FinanceLeaseAndOperatingLeaseLiability" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_FinanceLeaseRightOfUseAssetGross" abstract="false" name="FinanceLeaseRightOfUseAssetGross" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_AdditionalInLicenseAgreementsAndOtherArrangementsMember" abstract="true" name="AdditionalInLicenseAgreementsAndOtherArrangementsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_OperatingLossAndTaxCreditCarryforwardsTable" abstract="true" name="OperatingLossAndTaxCreditCarryforwardsTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CollaborativeandRoyaltyMember" abstract="true" name="CollaborativeandRoyaltyMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_CatalystBiosciencesMember" abstract="true" name="CatalystBiosciencesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_MammothBiosciencesIncMember" abstract="true" name="MammothBiosciencesIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_SanDiegoLeaseMember" abstract="true" name="SanDiegoLeaseMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementOptionPayment" abstract="false" name="CollaborativeArrangementOptionPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareRepurchaseProgram2021Member" abstract="true" name="ShareRepurchaseProgram2021Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_NumberOfApprovedGeneTherapyMedicines" abstract="false" name="NumberOfApprovedGeneTherapyMedicines" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_CommonStockPreferredStockAndEquityPlansDisclosureTextBlock" abstract="false" name="CommonStockPreferredStockAndEquityPlansDisclosureTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_ShareRepurchaseProgram2023Member" abstract="true" name="ShareRepurchaseProgram2023Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_MilestonePayableCurrent" abstract="false" name="MilestonePayableCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationByShareBasedPaymentAwardPercentofAwardsinTranche" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardPercentofAwardsinTranche" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:percentItemType"/>
  <xs:element id="vrtx_LloydsPharmacyMember" abstract="true" name="LloydsPharmacyMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_DebtandEquitySecuritiesUnrealizedLoss" abstract="false" name="DebtandEquitySecuritiesUnrealizedLoss" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_AuditInformationAbstract" abstract="true" name="AuditInformationAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestonePaymentsMaximum" abstract="false" name="CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestonePaymentsMaximum" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementMilestonePayment" abstract="false" name="CollaborativeArrangementMilestonePayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CloudComputingServiceContractsPolicyTextBlock" abstract="false" name="CloudComputingServiceContractsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:textBlockItemType"/>
  <xs:element id="vrtx_OtherCountriesOutsideoftheUnitedStatesandtheUnitedKingdomMember" abstract="true" name="OtherCountriesOutsideoftheUnitedStatesandtheUnitedKingdomMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types1:domainItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestoneAdditionalPaymentsMaximum" abstract="false" name="CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestoneAdditionalPaymentsMaximum" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
</xs:schema>
