Few studies have evaluated the clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS). Particularly, limited data exist comparing the results of TAVR with new-generation devices versus early-generation devices.This study sought to evaluate the clinical outcomes of TAVR for bicuspid AS with early- and new-generation devices.The Bicuspid TAVR Registry is an international multicenter study enrolling consecutive patients with bicuspid AS undergoing TAVR between April 2005 and May 2015.Of 301 patients, 199 patients (71.1%) were treated with early-generation devices (Sapien XT [Edwards Lifesciences Corporation, Irvine, California]: n = 87; CoreValve [Medtronic, Minneapolis, Minnesota]: n = 112) and 102 with new-generation devices (Sapien 3 [Edwards Lifesciences Corporation]: n = 91; Lotus [Boston Scientific Corporation, Marlborough, Massachusetts]: n = 11). The mean Society of Thoracic Surgeons score was 4.7 ± 5.2 without significant differences between groups (4.6 ± 5.1 vs. 4.9 ± 5.4; p = 0.57). Overall, all-cause mortality rates were 4.3% at 30 days and 14.4% at 1 year. Moderate or severe paravalvular leak was absent and significantly less frequent with new-generation compared to early-generation devices (0.0% vs. 8.5%; p = 0.002), which resulted in a higher device success rate (92.2% vs. 80.9%; p = 0.01). There were no differences between early- and new-generation devices in stroke (2.5% vs. 2.0%; p > 0.99), life-threatening bleeding (3.5% vs. 2.9%; p > 0.99), major vascular complication (4.5% vs. 2.9%; p = 0.76), stage 2 to 3 acute kidney injury (2.5% vs. 2.9%; p > 0.99), early safety endpoints (15.1% vs. 10.8%; p = 0.30), and 30-day all-cause mortality (4.5% vs. 3.9%; p > 0.99).The clinical outcomes of TAVR in patients with bicuspid AS were favorable. New-generation devices were associated with less paravalvular leak and, hence, a higher device success rate than early-generation devices. (The Bicuspid Aortic Stenosis Following Transcatheter Aortic Valve Replacement Registry [Bicuspid TAVR]; NCT02394184).