OBJECTIVES: The aim of this study was to determine whether transcatheter aortic valve replacement (TAVR) with the mechanically expanded Lotus valve (Boston Scientific, Natick Massachusetts) offers potential benefits over treatment with the self-expanding CoreValve (Medtronic, Minneapolis, Minnesota). BACKGROUND: New-generation transcatheter aortic valve systems are emerging in clinical trials and practice with design features aimed at improving safety and efficacy. To date, these devices have not been compared systematically with current-generation devices. METHODS: A total of 100 patients (83.4 +/- 4.8 years of age, 44 male, Society of Thoracic Surgeons Predicted Risk of Mortality score of 5.5 +/- 2.4) were assessed. Fifty consecutive patients undergoing a Lotus transcatheter aortic valve replacement were enrolled and compared with 50 matched patients treated with a CoreValve. An independent core laboratory reviewed all echocardiographic data, and an independent clinical events committee adjudicated all events. RESULTS: Valve Academic Research Consortium 2-defined device success was 84 and 64 in the Lotus and CoreValve cohorts, respectively (p = 0.02). This difference was driven by lower rates of moderate or greater aortic regurgitation (4 vs. 16.7 , respectively; p = 0.04) and higher rates of successfully implanting a single device in the correct anatomic position (100 vs. 86 , respectively; p = 0.06). Cardiovascular mortality rate (0 vs. 4 , respectively; p = 0.32), major stroke rate (4 vs. 2 , respectively; p = 0.56), and permanent pacemaker insertion rate (28 vs. 18 , respectively; p = 0.23) were not different at 30 days in the Lotus and CoreValve cohorts. CONCLUSIONS: In this matched comparison of high surgical risk patients undergoing transcatheter aortic valve replacement, the use of the Lotus device was associated with higher rates of Valve Academic Research Consortium 2-defined device success compared with the CoreValve. This was driven by higher rates of correct anatomic positioning and lower incidences of moderate paraprosthetic regurgitation. The clinical significance of these differences needs to be tested in a large randomized, controlled trial.