OBJECTIVES: Transcatheter aortic valve implantation (TAVI) represents an innovative technology superior to medical management (PARTNER study, US) in inoperable patients with severe aortic valve stenosis (AVS). This study aims to estimate the cost-effectiveness of TAVI compared to conservative medical management in symptomatic AVS patients in Spain. METHODS: A economic longitudinal cohort model was used to predict clinical and economic outcomes of symptomatic AVS patients treated with either transapical (TA) or transfemoral (TF) TAVI, or medical management alone (MEDICAL). Clinical model input data for TAVI was derived from the real-world SOURCE registry, and for MEDICAL from literature and a registry of 60 untreated Spanish AVS patients followed up for 336 days. Health utilities as well as resource use and unit costs utilized for modelling are representative for Spain. Missing information was substituted by expert estimates. Economic results are expressed as cost per quality adjusted life year (QALY) gained. Perspective is that of the national health system (NHS). Benefits and costs were discounted with 3% per year. RESULTS: Over the 3 year analysis period, 2.12 life years per patient were achieved with TA TAVI, 2.31 with TF TAVI and 1.51 with conservative medical care, representing. 1.24, 1.38 and 0.74 QALYs, respectively. Cumulative direct costs were predicted to amount to €37,311 and €35,689 with TA and TF TAVI, respectively and to €23,103 with conservative care. Cost/QALY gained was €28,003 for TA TAVI and €19,499 for TF TAVI, both ratios remaining well below the accepted willingness-to-pay threshold for Spain. The substantial cost of the TAVI procedure was largely offset over time mainly by savings related to prevented hospital readmissions for cardiac reasons. Sensitivity analyses indicated these findings to be robust. CONCLUSIONS: Compared to conservative management, TAVI is a life-saving and cost-effective treatment for high-risk or inoperable patients with symptomatic aortic valve stenosis in Spain.