Objective Stroke telemedicine improves the provision of reperfusion therapies in regional hospitals, yet evidence of its cost-effectiveness using patient-level data is lacking. The aim of this study was to estimate the cost per quality-adjusted life year (QALY) gained from stroke telemedicine. Methods As part of the Victorian Stroke Telemedicine (VST) program, stroke telemedicine provided to 16 hospitals in regional Victoria was evaluated using a historical-control design. Patient-level costs from a societal perspective (2018 Australian dollars (A))andQALYsupto12 monthsafterstrokewereestimatedusingdatafrommedicalrecords,surveysat3 monthsand12 monthsafterstrokeandmultipleimputation.Multivariableregressionmodelsandbootstrappingwereusedtoestimatedifferencesbetweenperiods.ResultsCostsandhealthoutcomeswereestimatedfrom1024confirmedstrokessufferedbypatientsarrivingathospitalwithin4.5 hofstrokeonset(medianage76 years,5582 449 per person for the control period and A82 259intheinterventionperiod(P= 0.986).QALYsat12 monthswereestimatedtobe0.43perpersonforthecontrolperiodand0.5perpersonintheinterventionperiod(P= 0.02).Following1000iterationsofbootstrapping,incomparisontothecontrolperiod,theVSTinterventionwasmoreeffectiveandcostsavingin50.60 and A$50 000 per QALY gained) in 10.4% of iterations. Conclusion The VST program was likely to be cost saving or cost-effective. Our findings provide confidence in supporting wider implementation of telemedicine for acute stroke care in Australia.</jats:p