OBJECTIVES: To fill the knowledge gap of cost-effectiveness result between randomized clinical trials and real world practice in treating patients with medically managed severe aortic stenosis, a hybrid comparison model, using a US societal perspective, was conducted.    METHODS: The cost-effectiveness of Transcatheter Aortic Valve Replacement (TAVR) was compared to medical management using the 2010 PARTNER trial (Cohort B) result and 2003 Medicare claims analysis (comparison group) on a population with severe aortic stenosis (AS). Survival rate, quality of life , medical resource use and related hospital and physician cost were reported in the PARTNER trial. The Medicare claims analysis presented survival rate and overall cost in treating severe AS, which was converted to 2010 dollars. To calculate quality-adjusted life expectancy, and estimate the incremental cost-effectiveness, QALY for Medicare claims analysis was derived from the control arm of PARTNER trial. The effect of uncertainty in model parameters was examined through one way sensitivity analysis and probabilistic sensitivity analysis (PSA). RESULTS: Over a two-year time horizon, in the base case the cost of TAVR was higher than the comparison group by $65,813. An additional 0.5 quality-adjusted life years was gained in the TAVR group. The resultant incremental cost-effectiveness ratio (ICER) was $ 132,155 per QALY gained for patients treated with TAVR vs. managed medically. Given $150,000 as the acceptability threshold for ICER willingness to pay, 66.4% iterations in PSA were favorable toward TAVR. CONCLUSIONS: In real world practice where it is difficult to qualify patients with rigid criteria, our result shows that TAVR fell at the borderline of the cost effectiveness acceptability threshold. Although this study only considers the first two years of treatment, given the relatively short 2-3 year life expectancy of medically managed patients with severe AS, this result highlights the importance to have a strict guideline  for TAVR to ensure its cost effectiveness.