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  <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_TRIKAFTAKAFTRIOMember" abstract="true" name="TRIKAFTAKAFTRIOMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_ScheduleofUnrecognizedSharebasedCompensationExpenseTableTextBlock" abstract="false" name="ScheduleofUnrecognizedSharebasedCompensationExpenseTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_LeaseAgreementsNumberOfBuildings" abstract="false" name="LeaseAgreementsNumberOfBuildings" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestoneAdditionalPaymentsMaximum" abstract="false" name="CollaborativeArrangementDevelopmentAndRegulatoryPotentialMilestoneAdditionalPaymentsMaximum" 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_MarketableSecuritiesAndOtherNoncurrentAssetsMember" abstract="true" name="MarketableSecuritiesAndOtherNoncurrentAssetsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_ShareBasedCompensationbyShareBasedPaymentAwardPerformancePeriod" abstract="false" name="ShareBasedCompensationbyShareBasedPaymentAwardPerformancePeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="vrtx_LeaseAgreementNumberOfLeases" abstract="false" name="LeaseAgreementNumberOfLeases" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="vrtx_CloudComputingServiceContractsPolicyTextBlock" abstract="false" name="CloudComputingServiceContractsPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types: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_CollaborativeArrangementUpFrontLicenseFee" abstract="false" name="CollaborativeArrangementUpFrontLicenseFee" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="vrtx_ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesTable" abstract="true" name="ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <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_EffectiveIncomeTaxRateReconciliationIntercompanyReceivableWriteOffPercent" abstract="false" name="EffectiveIncomeTaxRateReconciliationIntercompanyReceivableWriteOffPercent" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_CollaborativeArrangementsByAgreementAxis" abstract="true" name="CollaborativeArrangementsByAgreementAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesLineItems" abstract="true" name="ScheduleOfCashCashEquivalentsAndAvailableForSaleSecuritiesLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <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_FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueYearFour" abstract="false" name="FinanceLeaseAndOperatingLeaseLiabilityPaymentsDueYearFour" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" 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_ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMinimum" abstract="false" name="ShareBasedCompensationByShareBasedPaymentAwardAwardPercentageOfTargetMinimum" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="vrtx_AccredoHealthGroupIncMember" abstract="true" name="AccredoHealthGroupIncMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_VerveMember" abstract="true" name="VerveMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types: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_UnrecognizedTaxBenefitsDeferredTaxLiabilitiesGross" abstract="false" name="UnrecognizedTaxBenefitsDeferredTaxLiabilitiesGross" 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_ShareRepurchaseProgram2023Member" abstract="true" name="ShareRepurchaseProgram2023Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <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_CashFlowLesseeAbstract" abstract="true" name="CashFlowLesseeAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_WeightedAverageRemainingContractualLifeAbstract" abstract="true" name="WeightedAverageRemainingContractualLifeAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="vrtx_CostsAndExpensesMember" abstract="true" name="CostsAndExpensesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="vrtx_CatalystBiosciencesMember" abstract="true" name="CatalystBiosciencesMember" 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_ExercisePriceRangeFromDollars15001ToDollars20000Member" abstract="true" name="ExercisePriceRangeFromDollars15001ToDollars20000Member" 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_CollaborativeArrangementOptionPayment" abstract="false" name="CollaborativeArrangementOptionPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <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_LeaseSupplementalCashFlowInformationTableTextBlock" abstract="false" name="LeaseSupplementalCashFlowInformationTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <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_DebtandEquitySecuritiesUnrealizedGain" abstract="false" name="DebtandEquitySecuritiesUnrealizedGain" nillable="true" xbrli:periodType="instant" 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:schema>
