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

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2022 Workiva-->
<!--r:604ff4b8-e9c7-4650-8dd0-157166b40b78,g:4d54c5c0-9395-4dee-8c0f-cf03b20fca91-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:vrtx="http://www.vrtx.com/20211231" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types="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/20211231">
  <xs:import namespace="http://fasb.org/srt/2021-01-31" schemaLocation="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2021-01-31" schemaLocation="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.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://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/country/2021" schemaLocation="https://xbrl.sec.gov/country/2021/country-2021.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/currency/2021" schemaLocation="https://xbrl.sec.gov/currency/2021/currency-2021.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2021q4" schemaLocation="https://xbrl.sec.gov/dei/2021q4/dei-2021q4.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-20211231_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-20211231_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-20211231_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" 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-20211231_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="CoverPage" roleURI="http://www.vrtx.com/role/CoverPage">
        <link:definition>0001001 - Document - Cover Page</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>0002002 - 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="ConsolidatedStatementsofOperations" roleURI="http://www.vrtx.com/role/ConsolidatedStatementsofOperations">
        <link:definition>1001003 - Statement - Consolidated Statements of Operations</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>1002004 - 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>1003005 - 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>1004006 - 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>1005007 - 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>1006008 - 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>1007009 - 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>2101101 - 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="NatureofBusinessandAccountingPoliciesPolicies" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesPolicies">
        <link:definition>2202201 - 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>2303301 - 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="NatureofBusinessandAccountingPoliciesBusinessNarrativeDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesBusinessNarrativeDetails">
        <link:definition>2404401 - Disclosure - Nature of Business and Accounting Policies - Business Narrative (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>2405402 - 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>2406403 - 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="NatureofBusinessandAccountingPoliciesPropertyandEquipmentDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesPropertyandEquipmentDetails">
        <link:definition>2407404 - Disclosure - Nature of Business and Accounting Policies - 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>2408405 - 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="NatureofBusinessandAccountingPoliciesLeasesDetails" roleURI="http://www.vrtx.com/role/NatureofBusinessandAccountingPoliciesLeasesDetails">
        <link:definition>2409406 - Disclosure - Nature of Business and Accounting Policies - Leases (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="CollaborativeandOtherArrangements" roleURI="http://www.vrtx.com/role/CollaborativeandOtherArrangements">
        <link:definition>2110102 - Disclosure - Collaborative 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="CollaborativeandOtherArrangementsTables" roleURI="http://www.vrtx.com/role/CollaborativeandOtherArrangementsTables">
        <link:definition>2311302 - Disclosure - Collaborative and Other Arrangements (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="CollaborativeandOtherArrangementsAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/CollaborativeandOtherArrangementsAdditionalInformationDetails">
        <link:definition>2412407 - Disclosure - Collaborative and Other Arrangements - 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="CollaborativeandOtherArrangementsCRISPRTherapeuticsAGDetails" roleURI="http://www.vrtx.com/role/CollaborativeandOtherArrangementsCRISPRTherapeuticsAGDetails">
        <link:definition>2413408 - Disclosure - Collaborative and Other Arrangements - CRISPR Therapeutics AG (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="CollaborativeandOtherArrangementsKymeraModernaandOtherInLicenseAgreementsDetails" roleURI="http://www.vrtx.com/role/CollaborativeandOtherArrangementsKymeraModernaandOtherInLicenseAgreementsDetails">
        <link:definition>2414409 - Disclosure - Collaborative and Other Arrangements - Kymera, Moderna and Other In-License Agreements (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="CollaborativeandOtherArrangementsMerckKGaADetails" roleURI="http://www.vrtx.com/role/CollaborativeandOtherArrangementsMerckKGaADetails">
        <link:definition>2415410 - Disclosure - Collaborative and Other Arrangements - Merck KGaA (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="EarningsPerShare" roleURI="http://www.vrtx.com/role/EarningsPerShare">
        <link:definition>2116103 - 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="EarningsPerShareTables" roleURI="http://www.vrtx.com/role/EarningsPerShareTables">
        <link:definition>2317303 - 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="EarningsPerShareScheduleofComputationDetails" roleURI="http://www.vrtx.com/role/EarningsPerShareScheduleofComputationDetails">
        <link:definition>2418411 - 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="EarningsPerShareAntidilutiveSecuritiesDetails" roleURI="http://www.vrtx.com/role/EarningsPerShareAntidilutiveSecuritiesDetails">
        <link:definition>2419412 - Disclosure - Earnings Per Share - 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="FairValueMeasurements" roleURI="http://www.vrtx.com/role/FairValueMeasurements">
        <link:definition>2120104 - 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="FairValueMeasurementsTables" roleURI="http://www.vrtx.com/role/FairValueMeasurementsTables">
        <link:definition>2321304 - 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="FairValueMeasurementsAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/FairValueMeasurementsAdditionalInformationDetails">
        <link:definition>2422413 - 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="FairValueMeasurementsFinancialAssetsandLiabilitiesSubjecttoFairValueMeasurementsDetails" roleURI="http://www.vrtx.com/role/FairValueMeasurementsFinancialAssetsandLiabilitiesSubjecttoFairValueMeasurementsDetails">
        <link:definition>2423414 - Disclosure - Fair Value Measurements - 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="FairValueMeasurementsFairValueofContingentConsiderationLiabilitiesDetails" roleURI="http://www.vrtx.com/role/FairValueMeasurementsFairValueofContingentConsiderationLiabilitiesDetails">
        <link:definition>2424415 - Disclosure - Fair Value Measurements - 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="MarketableSecuritiesandEquityInvestments" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestments">
        <link:definition>2125105 - 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="MarketableSecuritiesandEquityInvestmentsTables" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsTables">
        <link:definition>2326305 - 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="MarketableSecuritiesandEquityInvestmentsAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsAdditionalInformationDetails">
        <link:definition>2427416 - 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="MarketableSecuritiesandEquityInvestmentsSummaryofCashEquivalentsandMarketableSecuritiesDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsSummaryofCashEquivalentsandMarketableSecuritiesDetails">
        <link:definition>2428417 - Disclosure - Marketable Securities and Equity Investments - Summary 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="MarketableSecuritiesandEquityInvestmentsSummaryofCashEquivalentsandMarketableSecuritiesDetails_1" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsSummaryofCashEquivalentsandMarketableSecuritiesDetails_1">
        <link:definition>2428417 - Disclosure - Marketable Securities and Equity Investments - Summary 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="MarketableSecuritiesandEquityInvestmentsAvailableforSaleDebtSecuritiesatFairValueDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsAvailableforSaleDebtSecuritiesatFairValueDetails">
        <link:definition>2429418 - Disclosure - Marketable Securities and Equity Investments - 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="MarketableSecuritiesandEquityInvestmentsAvailableforSaleDebtSecuritiesbyContractualMaturityDetails" roleURI="http://www.vrtx.com/role/MarketableSecuritiesandEquityInvestmentsAvailableforSaleDebtSecuritiesbyContractualMaturityDetails">
        <link:definition>2430419 - Disclosure - Marketable Securities and Equity Investments - 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="AccumulatedOtherComprehensiveIncomeLoss" roleURI="http://www.vrtx.com/role/AccumulatedOtherComprehensiveIncomeLoss">
        <link:definition>2131106 - 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="AccumulatedOtherComprehensiveIncomeLossTables" roleURI="http://www.vrtx.com/role/AccumulatedOtherComprehensiveIncomeLossTables">
        <link:definition>2332306 - 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="AccumulatedOtherComprehensiveIncomeLossDetails" roleURI="http://www.vrtx.com/role/AccumulatedOtherComprehensiveIncomeLossDetails">
        <link:definition>2433420 - 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="Hedging" roleURI="http://www.vrtx.com/role/Hedging">
        <link:definition>2134107 - 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="HedgingTables" roleURI="http://www.vrtx.com/role/HedgingTables">
        <link:definition>2335307 - 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="HedgingNarrativeDetails" roleURI="http://www.vrtx.com/role/HedgingNarrativeDetails">
        <link:definition>2436421 - Disclosure - Hedging - Narrative (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="HedgingNotionalAmountDetails" roleURI="http://www.vrtx.com/role/HedgingNotionalAmountDetails">
        <link:definition>2437422 - Disclosure - Hedging - 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="HedgingCashFlowHedgingInstrumentsDetails" roleURI="http://www.vrtx.com/role/HedgingCashFlowHedgingInstrumentsDetails">
        <link:definition>2438423 - Disclosure - Hedging - 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="HedgingDerivativeFairValueDetails" roleURI="http://www.vrtx.com/role/HedgingDerivativeFairValueDetails">
        <link:definition>2439424 - Disclosure - Hedging - 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="HedgingOffsettingDerivativesDetails" roleURI="http://www.vrtx.com/role/HedgingOffsettingDerivativesDetails">
        <link:definition>2440425 - Disclosure - Hedging - 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="Inventories" roleURI="http://www.vrtx.com/role/Inventories">
        <link:definition>2141108 - 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="InventoriesTables" roleURI="http://www.vrtx.com/role/InventoriesTables">
        <link:definition>2342308 - 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="InventoriesDetails" roleURI="http://www.vrtx.com/role/InventoriesDetails">
        <link:definition>2443426 - 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="PropertyandEquipment" roleURI="http://www.vrtx.com/role/PropertyandEquipment">
        <link:definition>2144109 - 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="PropertyandEquipmentTables" roleURI="http://www.vrtx.com/role/PropertyandEquipmentTables">
        <link:definition>2345309 - 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="PropertyandEquipmentPropertyandEquipmentNetDetails" roleURI="http://www.vrtx.com/role/PropertyandEquipmentPropertyandEquipmentNetDetails">
        <link:definition>2446427 - Disclosure - Property and Equipment - 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="PropertyandEquipmentNarrativeDetails" roleURI="http://www.vrtx.com/role/PropertyandEquipmentNarrativeDetails">
        <link:definition>2447428 - Disclosure - Property and Equipment - Narrative (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="IntangibleAssetsandGoodwill" roleURI="http://www.vrtx.com/role/IntangibleAssetsandGoodwill">
        <link:definition>2148110 - Disclosure - Intangible Assets and Goodwill</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="IntangibleAssetsandGoodwillDetails" roleURI="http://www.vrtx.com/role/IntangibleAssetsandGoodwillDetails">
        <link:definition>2449429 - Disclosure - 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="AdditionalBalanceSheetDetail" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetail">
        <link:definition>2150111 - 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="AdditionalBalanceSheetDetailTables" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailTables">
        <link:definition>2351310 - 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="AdditionalBalanceSheetDetailPrepaidExpensesandOtherCurrentAssetsDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailPrepaidExpensesandOtherCurrentAssetsDetails">
        <link:definition>2452430 - Disclosure - Additional Balance Sheet Detail - 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="AdditionalBalanceSheetDetailAccruedExpensesandOtherCurrentLiabilitiesDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailAccruedExpensesandOtherCurrentLiabilitiesDetails">
        <link:definition>2453431 - Disclosure - Additional Balance Sheet Detail - 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="AdditionalBalanceSheetDetailAdditionalCashFlowDetails" roleURI="http://www.vrtx.com/role/AdditionalBalanceSheetDetailAdditionalCashFlowDetails">
        <link:definition>2454432 - Disclosure - Additional Balance Sheet Detail - 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="Leases" roleURI="http://www.vrtx.com/role/Leases">
        <link:definition>2155112 - 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="LeasesTables" roleURI="http://www.vrtx.com/role/LeasesTables">
        <link:definition>2356311 - 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="LeasesAdditionalInformationDetails" roleURI="http://www.vrtx.com/role/LeasesAdditionalInformationDetails">
        <link:definition>2457433 - 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="LeasesComponentsofLeaseExpenseDetails" roleURI="http://www.vrtx.com/role/LeasesComponentsofLeaseExpenseDetails">
        <link:definition>2458434 - Disclosure - Leases - 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="LeasesBalanceSheetClassificationofLeaseAssetsandLiabilitiesDetails" roleURI="http://www.vrtx.com/role/LeasesBalanceSheetClassificationofLeaseAssetsandLiabilitiesDetails">
        <link:definition>2459435 - Disclosure - Leases - 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="LeasesMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails" roleURI="http://www.vrtx.com/role/LeasesMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails">
        <link:definition>2460436 - Disclosure - Leases - 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="LeasesMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_1" roleURI="http://www.vrtx.com/role/LeasesMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_1">
        <link:definition>2460436 - Disclosure - Leases - 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="LeasesMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_2" roleURI="http://www.vrtx.com/role/LeasesMaturitiesofOperatingandFinancingLeaseLiabilitiesDetails_2">
        <link:definition>2460436 - Disclosure - Leases - 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="LeasesWeightedAverageRemainingLeaseTermsandDiscountRatesDetails" roleURI="http://www.vrtx.com/role/LeasesWeightedAverageRemainingLeaseTermsandDiscountRatesDetails">
        <link:definition>2461437 - Disclosure - Leases - 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="LeasesSupplementalCashFlowInformationDetails" roleURI="http://www.vrtx.com/role/LeasesSupplementalCashFlowInformationDetails">
        <link:definition>2462438 - Disclosure - Leases - 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="CommonStockPreferredStockandEquityPlans" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlans">
        <link:definition>2163113 - 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="CommonStockPreferredStockandEquityPlansTables" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansTables">
        <link:definition>2364312 - 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="CommonStockPreferredStockandEquityPlansCommonStockandPreferredStockDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansCommonStockandPreferredStockDetails">
        <link:definition>2465439 - 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>2466440 - 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>2467441 - 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="CommonStockPreferredStockandEquityPlansOutstandingandVestedStockOptionsDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansOutstandingandVestedStockOptionsDetails">
        <link:definition>2468442 - Disclosure - Common Stock, Preferred Stock and Equity Plans - Outstanding and Vested Stock 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>2469443 - 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="CommonStockPreferredStockandEquityPlansRestrictedStockandRestrictedStockUnitsDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansRestrictedStockandRestrictedStockUnitsDetails">
        <link:definition>2470444 - 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>2471445 - 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="CommonStockPreferredStockandEquityPlansEmployeeStockPurchasePlanDetails" roleURI="http://www.vrtx.com/role/CommonStockPreferredStockandEquityPlansEmployeeStockPurchasePlanDetails">
        <link:definition>2472446 - 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>2473447 - 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="StockbasedCompensationExpense" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpense">
        <link:definition>2174114 - 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="StockbasedCompensationExpenseTables" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseTables">
        <link:definition>2375313 - 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="StockbasedCompensationExpenseDetails" roleURI="http://www.vrtx.com/role/StockbasedCompensationExpenseDetails">
        <link:definition>2476448 - Disclosure - 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="IncomeTaxes" roleURI="http://www.vrtx.com/role/IncomeTaxes">
        <link:definition>2177115 - 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="IncomeTaxesTables" roleURI="http://www.vrtx.com/role/IncomeTaxesTables">
        <link:definition>2378314 - 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="IncomeTaxesComponentsofIncomeandProvisionforBenefitfromIncomeTaxesDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesComponentsofIncomeandProvisionforBenefitfromIncomeTaxesDetails">
        <link:definition>2479449 - Disclosure - Income Taxes - 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="IncomeTaxesEffectiveIncomeTaxReconciliationDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesEffectiveIncomeTaxReconciliationDetails">
        <link:definition>2480450 - Disclosure - Income Taxes - 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="IncomeTaxesNarrativeDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesNarrativeDetails">
        <link:definition>2481451 - Disclosure - Income Taxes - Narrative (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="IncomeTaxesDeferredTaxAssetsandLiabilitiesDetails" roleURI="http://www.vrtx.com/role/IncomeTaxesDeferredTaxAssetsandLiabilitiesDetails">
        <link:definition>2482452 - Disclosure - Income Taxes - 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>2483453 - 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="CommitmentsandContingencies" roleURI="http://www.vrtx.com/role/CommitmentsandContingencies">
        <link:definition>2184116 - 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="CommitmentsandContingenciesRevolvingCreditFacilityDetails" roleURI="http://www.vrtx.com/role/CommitmentsandContingenciesRevolvingCreditFacilityDetails">
        <link:definition>2485454 - Disclosure - Commitments and Contingencies - Revolving Credit Facility (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="CommitmentsandContingenciesContingenciesDetails" roleURI="http://www.vrtx.com/role/CommitmentsandContingenciesContingenciesDetails">
        <link:definition>2486455 - Disclosure - Commitments and Contingencies - 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="SegmentInformation" roleURI="http://www.vrtx.com/role/SegmentInformation">
        <link:definition>2187117 - 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="SegmentInformationTables" roleURI="http://www.vrtx.com/role/SegmentInformationTables">
        <link:definition>2388315 - 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="SegmentInformationRevenuesbyProductDetails" roleURI="http://www.vrtx.com/role/SegmentInformationRevenuesbyProductDetails">
        <link:definition>2489456 - Disclosure - Segment Information - 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="SegmentInformationRevenuebyGeographicLocationDetails" roleURI="http://www.vrtx.com/role/SegmentInformationRevenuebyGeographicLocationDetails">
        <link:definition>2490457 - Disclosure - Segment Information - 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="SegmentInformationSignificantCustomersDetails" roleURI="http://www.vrtx.com/role/SegmentInformationSignificantCustomersDetails">
        <link:definition>2491458 - Disclosure - Segment Information - 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="SegmentInformationPropertyandEquipmentNetbyLocationDetails" roleURI="http://www.vrtx.com/role/SegmentInformationPropertyandEquipmentNetbyLocationDetails">
        <link:definition>2492459 - Disclosure - Segment Information - 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_LeaseAgreementsNumberOfBuildings" abstract="false" name="LeaseAgreementsNumberOfBuildings" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_KymeraTherapeuticsMember" abstract="true" name="KymeraTherapeuticsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CRISPRMember" abstract="true" name="CRISPRMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementRighttoLicenseNumberOfClinicalStagePrograms" abstract="false" name="CollaborativeArrangementRighttoLicenseNumberOfClinicalStagePrograms" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_PaymentToAcquirePreferredStockAndNotesReceivable" abstract="false" name="PaymentToAcquirePreferredStockAndNotesReceivable" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareRepurchaseProgram2019Member" abstract="true" name="ShareRepurchaseProgram2019Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_LesseeLeasingArrangementsCapitalLeasesTermofContract" abstract="false" name="LesseeLeasingArrangementsCapitalLeasesTermofContract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars3628ToDollars10000Member" abstract="true" name="ExercisePriceRangeFromDollars3628ToDollars10000Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementAgreementDomain" abstract="true" name="CollaborativeArrangementAgreementDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_LeaseSupplementalCashFlowInformationTableTextBlock" abstract="false" name="LeaseSupplementalCashFlowInformationTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_ScheduleOfStockAndStockOptionEquityPlansTableTextBlock" abstract="false" name="ScheduleOfStockAndStockOptionEquityPlansTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_PubliclyTradedCompaniesSaleMember" abstract="true" name="PubliclyTradedCompaniesSaleMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_WeightedAverageDiscountRateAbstract" abstract="true" name="WeightedAverageDiscountRateAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_TRIKAFTAKAFTRIOMember" abstract="true" name="TRIKAFTAKAFTRIOMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_EffectiveIncomeTaxRateReconciliationInterEntityTransferOfIntellectualPropertyRightsAmount" abstract="false" name="EffectiveIncomeTaxRateReconciliationInterEntityTransferOfIntellectualPropertyRightsAmount" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationAllocationAbstract" abstract="true" name="ShareBasedCompensationAllocationAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CashFlowLesseeAbstract" abstract="true" name="CashFlowLesseeAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <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_FinanceLeasesOtherCurrentLiabilities" abstract="false" name="FinanceLeasesOtherCurrentLiabilities" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <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_CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestonePaymentsMaximum" abstract="false" name="CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestonePaymentsMaximum" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementRightToLicenseNumberOfDevelopmentPrograms" abstract="false" name="CollaborativeArrangementRightToLicenseNumberOfDevelopmentPrograms" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <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_OtherCountriesOutsideoftheUnitedStatesandtheUnitedKingdomMember" abstract="true" name="OtherCountriesOutsideoftheUnitedStatesandtheUnitedKingdomMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_FinanceLeaseLiabilityTenantAllowance" abstract="false" name="FinanceLeaseLiabilityTenantAllowance" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <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_SemmaTherapeuticsInc.Member" abstract="true" name="SemmaTherapeuticsInc.Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_GoodwillAndIntangibleAssetsIndefiniteLivedAssetsPolicyTextBlock" abstract="false" name="GoodwillAndIntangibleAssetsIndefiniteLivedAssetsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_MerckKGaAMember" abstract="true" name="MerckKGaAMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesLineItems" abstract="true" name="ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_LloydsPharmacyMember" abstract="true" name="LloydsPharmacyMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CommonStockPreferredStockAndEquityPlansDisclosureTextBlock" abstract="false" name="CommonStockPreferredStockAndEquityPlansDisclosureTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="vrtx_ApolLo1BioLLCMember" abstract="true" name="ApolLo1BioLLCMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_ShareRepurchaseProgram2018Member" abstract="true" name="ShareRepurchaseProgram2018Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_LeaseAgreementNumberOfLeases" abstract="false" name="LeaseAgreementNumberOfLeases" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_ShareRepurchaseProgram2021Member" abstract="true" name="ShareRepurchaseProgram2021Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_OtherCountriesOutsideoftheUnitedStatesandEuropeMember" abstract="true" name="OtherCountriesOutsideoftheUnitedStatesandEuropeMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEligibleEmployeePurchasePricePercentageOfFairValue" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEligibleEmployeePurchasePricePercentageOfFairValue" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_MarketableSecuritiesMember" abstract="true" name="MarketableSecuritiesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars20001ToDollars28627Member" abstract="true" name="ExercisePriceRangeFromDollars20001ToDollars28627Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ScheduleofWeightedAverageRemainingLeaseTermsandDiscountRatesRelatedtoLeasesTableTextBlock" abstract="false" name="ScheduleofWeightedAverageRemainingLeaseTermsandDiscountRatesRelatedtoLeasesTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementRightToLicenseNumberOfTargets" abstract="false" name="CollaborativeArrangementRightToLicenseNumberOfTargets" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_StockandOptionPlan2013Member" abstract="true" name="StockandOptionPlan2013Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesTable" abstract="true" name="ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_LesseeOperatingLeaseLiabilityTenantAllowance" abstract="false" name="LesseeOperatingLeaseLiabilityTenantAllowance" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_AggregateIntrinsicValueAbstract" abstract="true" name="AggregateIntrinsicValueAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_AccredoCurascriptMember" abstract="true" name="AccredoCurascriptMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_Percentageofemployeeseligibleforaccelerationofequityawards" abstract="false" name="Percentageofemployeeseligibleforaccelerationofequityawards" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <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_FinanceLeasandOperatingLeaseLiabilitiesPaymentsDueAbstract" abstract="true" name="FinanceLeasandOperatingLeaseLiabilitiesPaymentsDueAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_SanDiegoLeaseMember" abstract="true" name="SanDiegoLeaseMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_McKessonCorporationMember" abstract="true" name="McKessonCorporationMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types: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_ShareBasedCompensationbyShareBasedPaymentAwardPerformancePeriod" abstract="false" name="ShareBasedCompensationbyShareBasedPaymentAwardPerformancePeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <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_NonFinancialPerformanceSharesMember" abstract="true" name="NonFinancialPerformanceSharesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_FinanceLeaseAndOperatingLeaseLiabilityTenantAllowance" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityTenantAllowance" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_EffectiveIncomeTaxRateReconciliationUncertianTaxPositionsPercent" abstract="false" name="EffectiveIncomeTaxRateReconciliationUncertianTaxPositionsPercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_DebtCovenantInterestCoverageRatio" abstract="false" name="DebtCovenantInterestCoverageRatio" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="vrtx_CollaborativeandRoyaltyMember" abstract="true" name="CollaborativeandRoyaltyMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_AuditInformationAbstract" abstract="true" name="AuditInformationAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMinimum" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMinimum" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_TaxCarryforwardsLineItems" abstract="true" name="TaxCarryforwardsLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_InnovationSquareLeaseMember" abstract="true" name="InnovationSquareLeaseMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementRighttoLicenseNumberOfPreClinicalStagePrograms" abstract="false" name="CollaborativeArrangementRighttoLicenseNumberOfPreClinicalStagePrograms" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementAllocationOfNetProfitsAndLossesPercent" abstract="false" name="CollaborativeArrangementAllocationOfNetProfitsAndLossesPercent" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_SharebasedCompensationArrangementbySharebasedPaymentAwardNumberofPurchasePeriods" abstract="false" name="SharebasedCompensationArrangementbySharebasedPaymentAwardNumberofPurchasePeriods" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_AmountofOptionalRenewalTerms" abstract="false" name="AmountofOptionalRenewalTerms" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <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_ORKAMBIMember" abstract="true" name="ORKAMBIMember" 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_CommonStockVotesPerEachShare" abstract="false" name="CommonStockVotesPerEachShare" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationByShareBasedPaymentAwardPercentofAwardsinTranche" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardPercentofAwardsinTranche" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_CashAndMoneyMarketFundsMember" abstract="true" name="CashAndMoneyMarketFundsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars10001ToDollars15000Member" abstract="true" name="ExercisePriceRangeFromDollars10001ToDollars15000Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_WalgreenCo.Member" abstract="true" name="WalgreenCo.Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ScheduleOfShareBasedCompensationArrangementByShareBasedPaymentAwardAwardTypeDomain" abstract="true" name="ScheduleOfShareBasedCompensationArrangementByShareBasedPaymentAwardAwardTypeDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ScheduleofUnrecognizedSharebasedCompensationExpenseTableTextBlock" abstract="false" name="ScheduleofUnrecognizedSharebasedCompensationExpenseTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_FinanceLeaseAndOperatingLeaseLiabilityPaymentDueYearThree" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentDueYearThree" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ProceedsFromFinanceLeases" abstract="false" name="ProceedsFromFinanceLeases" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_DeferredTaxAssetsMember" abstract="true" name="DeferredTaxAssetsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ArborBiotechnologiesIncMember" abstract="true" name="ArborBiotechnologiesIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_WeightedAverageRemainingLeaseAbstract" abstract="true" name="WeightedAverageRemainingLeaseAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <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_EmployeeStockPurchasePlanMember" abstract="true" name="EmployeeStockPurchasePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ShareRepurchaseProgram2020Member" abstract="true" name="ShareRepurchaseProgram2020Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ExercisePriceRangeFromDollars15001ToDollars20000Member" abstract="true" name="ExercisePriceRangeFromDollars15001ToDollars20000Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_NumberOfCreditAgreements" abstract="false" name="NumberOfCreditAgreements" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_ScheduleOfShareBasedCompensationArrangementByShareBasedPaymentAwardAwardTypeAxis" abstract="true" name="ScheduleOfShareBasedCompensationArrangementByShareBasedPaymentAwardAwardTypeAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ModernaAgreementMember" abstract="true" name="ModernaAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_OperatingLossAndTaxCreditCarryforwardsTable" abstract="true" name="OperatingLossAndTaxCreditCarryforwardsTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <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_FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueAfterYearFive" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueAfterYearFive" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_UnrecognizedTaxBenefitsTable" abstract="true" name="UnrecognizedTaxBenefitsTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CRISPRTherapeuticsAGMember" abstract="true" name="CRISPRTherapeuticsAGMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_MolecularTemplatesIncMember" abstract="true" name="MolecularTemplatesIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_SkyhawkTherapeuticsIncMember" abstract="true" name="SkyhawkTherapeuticsIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_UnrecognizedTaxBenefitsLineItems" abstract="true" name="UnrecognizedTaxBenefitsLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_KalydecoMember" abstract="true" name="KalydecoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_DeferredTaxAssetsAccruedExpensesAndOther" abstract="false" name="DeferredTaxAssetsAccruedExpensesAndOther" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_DebtCovenantIncreaseInConsolidatedLeverageRatio" abstract="false" name="DebtCovenantIncreaseInConsolidatedLeverageRatio" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="vrtx_SharebasedCompensationArrangementbySharebasedPaymentAwardDurationofPurchasePeriod" abstract="false" name="SharebasedCompensationArrangementbySharebasedPaymentAwardDurationofPurchasePeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementInvestmentinCollaborativePartnerAmount" abstract="false" name="CollaborativeArrangementInvestmentinCollaborativePartnerAmount" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_MammothBiosciencesIncMember" abstract="true" name="MammothBiosciencesIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CRISPRDMDDM1Member" abstract="true" name="CRISPRDMDDM1Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_DebtCovenantConsolidatedLeverageRatio" abstract="false" name="DebtCovenantConsolidatedLeverageRatio" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <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_WeightedAverageRemainingContractualLifeAbstract" abstract="true" name="WeightedAverageRemainingContractualLifeAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementResearchAndDevelopmentExpenses" abstract="false" name="CollaborativeArrangementResearchAndDevelopmentExpenses" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_EffectiveIncomeTaxRateReconciliationIntercompanyReceivableWriteOffPercent" abstract="false" name="EffectiveIncomeTaxRateReconciliationIntercompanyReceivableWriteOffPercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_OutsidetheUnitedStatesMember" abstract="true" name="OutsidetheUnitedStatesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_AssetsAndLiabilitiesLesseeTableTextBlock" abstract="false" name="AssetsAndLiabilitiesLesseeTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="vrtx_InProcessResearchAndDevelopmentAssetsAndContingentPaymentsPolicyTextBlock" abstract="false" name="InProcessResearchAndDevelopmentAssetsAndContingentPaymentsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementsByAgreementAxis" abstract="true" name="CollaborativeArrangementsByAgreementAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMaximum" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMaximum" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_CRSIPRARJDCAMember" abstract="true" name="CRSIPRARJDCAMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types: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_RightOfUseAssetObtainedInExchangeForLeaseLiabilityAbstract" abstract="true" name="RightOfUseAssetObtainedInExchangeForLeaseLiabilityAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOutstandingNumber" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOutstandingNumber" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <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_LineOfCreditFacilityAdditionalBorrowingCapacity" abstract="false" name="LineOfCreditFacilityAdditionalBorrowingCapacity" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_LesseeLeasingArrangementsCapitalLeasesRenewalTerm" abstract="false" name="LesseeLeasingArrangementsCapitalLeasesRenewalTerm" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_StockAndOptionPlan2006Member" abstract="true" name="StockAndOptionPlan2006Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_EffectiveIncomeTaxRateReconciliationInterEntityTransferOfIntellectualPropertyRightsPercent" abstract="false" name="EffectiveIncomeTaxRateReconciliationInterEntityTransferOfIntellectualPropertyRightsPercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_LesseeOperatingLeaseNumberOfRenewalOptions" abstract="false" name="LesseeOperatingLeaseNumberOfRenewalOptions" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <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_FinancialPerformanceSharesMember" abstract="true" name="FinancialPerformanceSharesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_SYMDEKOSYMKEVIMember" abstract="true" name="SYMDEKOSYMKEVIMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ExonicsTherapeuticsMember" abstract="true" name="ExonicsTherapeuticsMember" 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-types:domainItemType"/>
  <xs:element id="vrtx_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationTableTextBlock" abstract="false" name="IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_BusinessCombinationRemainingMilestonePayment" abstract="false" name="BusinessCombinationRemainingMilestonePayment" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfInstallments" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfInstallments" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
</xs:schema>
