Background: Transfemoral transcatheter aortic valve replacement (TAVR) is cost-effective for management of severe aortic stenosis (AS) in patients with unacceptable risk for aortic valve replacement (AVR). However, the relative cost-effectiveness of TAVR and tissue AVR is ill-defined in high-risk patients where surgery is an option. We developed a Markov model to inform the choice between transfemoral TAVR and AVR in high-risk patients. Methods: A Markov model was developed to examine the progression of patients between health states, defined as peri- and post-procedural, post-complication, and death. The mean and variance of risks, transition probabilities, utilities and cost of TAVR and AVR were derived from meta-analysis of relevant registries, studies and trials. Outcome and cost were derived from 10,000 simulations. Sensitivity analyses were based on the likelihood of mortality, stroke, and other commonly observed outcomes. Further analyses evaluated situations thought to favor tissue AVR or TAVR. Results: In the reference case (age 80, peri-operative mortality of transfemoral TAVR and AVR 5.8 vs 9.1%, annual mortality 22.2 vs 22.5%), the utility of TAVR was greater than AVR (1.71 vs 1.64 QALY). As the cost of TAVR was greater than AVR ($26,176 vs $19,361), the incremental cost-effectiveness ratio (ICER) was $97,357/QALY. In sensitivity analyses, variations in stroke, peri-operative and annual mortality are the main drivers of variation in health outcomes. The current risk profile of transfemoral TAVR offered net health benefits when peri-operative AVR mortality was >5.2%, or stroke post-TAVR was <11.3% (Figure). In a scenario analysis based only on operable PARTNER patients (Cohort A), QALYs for TAVR and AVR were 1.69 and 1.63, with an ICER of $70,633/QALY. Conclusion: TAVR may provide net health benefits at acceptable cost in selected high-risk patients among whom AVR is the current procedure of choice.