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  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesOutstandingBeginning" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesOutstandingBeginning"/>
  <xs:element name="GrantDateFairValueOutstandingBeginning" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrantDateFairValueOutstandingBeginning"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesGranted" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesGranted"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueGranted" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueGranted"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesVestedAndIssued" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsSharesVestedAndIssued"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueVestedAndIssued" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueVestedAndIssued"/>
  <xs:element name="SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueOutstandingEnding" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharebasedCompensationArrangementBySharebasedPaymentRestrictedStockAwardsWeightedAverageGrantDateFairValueOutstandingEnding"/>
  <xs:element name="GrantDateFairValueForfeited" type="dtr:perShareItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrantDateFairValueForfeited"/>
  <xs:element name="TotalLeaseLiabilities" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_TotalLeaseLiabilities"/>
  <xs:element name="ConcentrationRiskPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ConcentrationRiskPercentage"/>
  <xs:element name="FederalIncomeTaxStateTaxEffectNetOfFederalBenefit" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxStateTaxEffectNetOfFederalBenefit"/>
  <xs:element name="FederalIncomeTaxStateRateChange" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxStateRateChange"/>
  <xs:element name="FederalIncomeTaxChangeInFairValueOfContingentConsideration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxChangeInFairValueOfContingentConsideration"/>
  <xs:element name="FederalIncomeTaxOptionExerciseBenefitsNetOfSection162MLimitations" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxOptionExerciseBenefitsNetOfSection162MLimitations"/>
  <xs:element name="FederalIncomeTaxOtherPermanentItems" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxOtherPermanentItems"/>
  <xs:element name="FederalIncomeTaxOtherAdjustments" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxOtherAdjustments"/>
  <xs:element name="FederalIncomeTaxNetOperatingLossExpiring" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxNetOperatingLossExpiring"/>
  <xs:element name="FederalIncomeTaxExpensesBenefitValueAllowance" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FederalIncomeTaxExpensesBenefitValueAllowance"/>
  <xs:element name="DeferredTaxAssetsOperatingLeaseLiability" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxAssetsOperatingLeaseLiability"/>
  <xs:element name="DeferredTaxLiabilitiesOperatingLeaseRightOfUseAssets" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxLiabilitiesOperatingLeaseRightOfUseAssets"/>
  <xs:element name="DeferredTaxAssetNetOfValuationAllowance" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredTaxAssetNetOfValuationAllowance"/>
  <xs:element name="USHealthcareProvidersPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_USHealthcareProvidersPercentage"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_SummaryofSignificantAccountingPoliciesDetailsTable"/>
  <xs:element name="SummaryofSignificantAccountingPoliciesDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SummaryofSignificantAccountingPoliciesDetailsLineItems"/>
  <xs:element name="DeferredRevenueDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_DeferredRevenueDetailsTable"/>
  <xs:element name="DeferredRevenueDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DeferredRevenueDetailsLineItems"/>
  <xs:element name="OptionsGrantedToAcquireExclusivePatentRights" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OptionsGrantedToAcquireExclusivePatentRights"/>
  <xs:element name="ContingentPurchasePriceDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_ContingentPurchasePriceDetailsTable"/>
  <xs:element name="ContingentPurchasePriceDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ContingentPurchasePriceDetailsLineItems"/>
  <xs:element name="ContingentPaymentInCash" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ContingentPaymentInCash"/>
  <xs:element name="ContingentEquityFairValueDisclosure" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_ContingentEquityFairValueDisclosure"/>
  <xs:element name="MinimumPaymentForContingent" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_MinimumPaymentForContingent"/>
  <xs:element name="FairValueOfRiskFreeRateOfReturn" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_FairValueOfRiskFreeRateOfReturn"/>
  <xs:element name="FairValueOfTerm" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_FairValueOfTerm"/>
  <xs:element name="FairValueOfVolatility" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_FairValueOfVolatility"/>
  <xs:element name="PaymentOfShareholderLiability" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PaymentOfShareholderLiability"/>
  <xs:element name="PaymentForLiability" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PaymentForLiability"/>
  <xs:element name="StockholdersEquityDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_StockholdersEquityDetailsTable"/>
  <xs:element name="StockholdersEquityDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockholdersEquityDetailsLineItems"/>
  <xs:element name="IssuanceOfCommonStockExerciseValue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_IssuanceOfCommonStockExerciseValue"/>
  <xs:element name="PaymentsToAdvisorsAndLegalFees" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_PaymentsToAdvisorsAndLegalFees"/>
  <xs:element name="GrossProceedsOfCommonStockAmount" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_GrossProceedsOfCommonStockAmount"/>
  <xs:element name="StockCompensationDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_StockCompensationDetailsTable"/>
  <xs:element name="StockCompensationDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_StockCompensationDetailsLineItems"/>
  <xs:element name="ShareBasedCompensationArrangementBySharesBasedPaymentsAwardOptionsExercisableNumber" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_ShareBasedCompensationArrangementBySharesBasedPaymentsAwardOptionsExercisableNumber"/>
  <xs:element name="SharesOfCommonStockUnderlyingRestrictedStockUnitAwards" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharesOfCommonStockUnderlyingRestrictedStockUnitAwards"/>
  <xs:element name="PercentageOfFairMarketValueOfCommonstock" type="dtr:percentItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="oprx_PercentageOfFairMarketValueOfCommonstock"/>
  <xs:element name="SharesBasedCompensationArrangementBySharesBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_SharesBasedCompensationArrangementBySharesBasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
  <xs:element name="RestrictedStockUnitsIssued" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RestrictedStockUnitsIssued"/>
  <xs:element name="VestedPriceUnitsDescription" type="xbrli:stringItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_VestedPriceUnitsDescription"/>
  <xs:element name="LeasesDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_LeasesDetailsTable"/>
  <xs:element name="LeasesDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LeasesDetailsLineItems"/>
  <xs:element name="OperatingLeasesExpiresPeriod" type="xbrli:dateItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeasesExpiresPeriod"/>
  <xs:element name="OperatingLeasesRentPayable" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeasesRentPayable"/>
  <xs:element name="MeasurementOfLeaseLiabilities" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_MeasurementOfLeaseLiabilities"/>
  <xs:element name="OperatingLeaseRightOfUseAssetAmortization" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_OperatingLeaseRightOfUseAssetAmortization"/>
  <xs:element name="MajorCustomersandVendorsDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_MajorCustomersandVendorsDetailsTable"/>
  <xs:element name="MajorCustomersandVendorsDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_MajorCustomersandVendorsDetailsLineItems"/>
  <xs:element name="CommitmentsandContingentLiabilitiesDetailsTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="oprx_CommitmentsandContingentLiabilitiesDetailsTable"/>
  <xs:element name="CommitmentsandContingentLiabilitiesDetailsLineItems" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CommitmentsandContingentLiabilitiesDetailsLineItems"/>
  <xs:element name="UnderpaymentPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_UnderpaymentPercentage"/>
  <xs:element name="FutureMinimumPayments" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="oprx_FutureMinimumPayments"/>
  <xs:element name="MinimumPaymentsDue" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="oprx_MinimumPaymentsDue"/>
  <xs:element name="CareSpeakCommunicationsIncMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CareSpeakCommunicationsIncMember"/>
  <xs:element name="CurrentMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CurrentMember"/>
  <xs:element name="CustomerAMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerAMember"/>
  <xs:element name="CustomerBMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerBMember"/>
  <xs:element name="CustomerCMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerCMember"/>
  <xs:element name="CustomerFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerFourMember"/>
  <xs:element name="CustomerOneMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerOneMember"/>
  <xs:element name="CustomerThreeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerThreeMember"/>
  <xs:element name="CustomerTwoMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_CustomerTwoMember"/>
  <xs:element name="ExercisePriceRangeFiveMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeFiveMember"/>
  <xs:element name="ExercisePriceRangeFourMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeFourMember"/>
  <xs:element name="ExercisePriceRangeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeMember"/>
  <xs:element name="ExercisePriceRangeOneMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeOneMember"/>
  <xs:element name="ExercisePriceRangeThreeMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeThreeMember"/>
  <xs:element name="ExercisePriceRangeTwoMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_ExercisePriceRangeTwoMember"/>
  <xs:element name="KeyPartnersMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_KeyPartnersMember"/>
  <xs:element name="LongTermMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_LongTermMember"/>
  <xs:element name="OneEntitiesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_OneEntitiesMember"/>
  <xs:element name="PartnerAMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PartnerAMember"/>
  <xs:element name="PartnerBMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_PartnerBMember"/>
  <xs:element name="RMDYHealthMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RMDYHealthMember"/>
  <xs:element name="RMDYHealthShareholdersMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_RMDYHealthShareholdersMember"/>
  <xs:element name="TotalOptionOutstandingMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TotalOptionOutstandingMember"/>
  <xs:element name="TwoEntitiesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_TwoEntitiesMember"/>
  <xs:element name="VestedOptionsOutstandingMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_VestedOptionsOutstandingMember"/>
  <xs:element name="DocumentAndEntityInformationAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="oprx_DocumentAndEntityInformationAbstract"/>
</xs:schema>
