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Summary Objectives Transcatheter aortic valve implantation (TAVI) has become the standard of care for inoperable patients with severe aortic stenosis and is an alternative to conventional surgery for high-risk aortic valve replacement (AVR) patients. There is a positive correlation between severity of pre-operative patients and hospital costs. The aim of this study was to compare empirically derived costs of the two therapies in South Africa. Methods The cost-comparison analysis was performed with a MediClinic database including 239 conventional isolated AVR (cAVR) and 75 TAVI cases. All costs are given in 2011 ZAR. The subset of cAVR patients were derived from the relevant and available information in the database and their costs were compared with TAVI costs. Results From the 75 available subjects, mean TAVI costs were ZAR 335.5k ± 47.9k, (median ZAR 326.5k) with a mean (median) ICU and hospital length of stay (LoS) of 2.7 (2.0) and 7.6 (6.5) days, respectively. The mean cAVR cost was lower at ZAR 213.9 ± 87.5k (median ZAR 193.6k) but this included the entire population costs (i.e. low to high surgical risk). When estimating cAVR costs, defined by LoS of more than six and 13 days in the ICU and hospital, respectively, and being over 75 years of age, the estimate increased to ZAR 337.9k, which was above the TAVI mean costs. In-hospital mortality was 5.3 and 7.9% for TAVI and the entire cAVR group, respectively. When considering the subset of cAVR patients most likely to be high risk, it increased to 21.4%. Conclusions Within the context of limited clinical data we performed the first attempt at cost-effective analysis of TAVI vs cAVR in South Africa. Treatment of aortic stenosis with cAVR in a post hoc defined high-risk patient segment was more expensive than TAVI in South African centres. Despite common perceptions on costs, adoption of TAVI as an alternative, less-invasive therapy that has been clinically proven and recommended by an FDA advisory panel (Partner A) to be at least as effective as cAVR, has a viable economic argument in appropriate patients.