Abstract Background Early experience with transcatheter aortic valve replacement (TAVR) within failed bioprosthetic surgical aortic valves has shown that valve-in-valve (VIV) TAVR is a feasible therapeutic option with acceptable acute procedural results. Objectives The authors examined 30-day and 1-year outcomes in a large cohort of high-risk patients undergoing VIV TAVR. Methods Patients with symptomatic degeneration of surgical aortic bioprostheses at high risk (≥50% major morbidity or mortality) for reoperative surgery were prospectively enrolled in the multicenter PARTNER (Placement of Aortic Transcatheter Valves) 2 VIV trial and continued access registries. Results Valve-in-valve procedures were performed in 365 patients (96 initial registry, 269 continued access patients). Mean age was 78.9 ± 10.2 years, and mean Society of Thoracic Surgeons score was 9.1 ± 4.7%. At 30 days, all-cause mortality was 2.7%, stroke was 2.7%, major vascular complication was 4.1%, conversion to surgery was 0.6%, coronary occlusion was 0.8%, and new pacemaker insertion was 1.9%. One-year all-cause mortality was 12.4%. Mortality fell from the initial registry to the subsequent continued access registry, both at 30 days (8.2% vs. 0.7%, respectively; p = 0.0001) and at 1 year (19.7% vs. 9.8%, respectively; p = 0.006). At 1 year, mean gradient was 17.6 mm Hg, and effective orifice area was 1.16 cm2 , with greater than mild paravalvular regurgitation of 1.9%. Left ventricular ejection fraction increased (50.6% to 54.2%), and mass index decreased (135.7 to 117.6 g/m2 ), with reductions in both mitral (34.9% vs. 12.7%) and tricuspid (31.8% vs. 21.2%) moderate or severe regurgitation (all p < 0.0001). Kansas City Cardiomyopathy Questionnaire score increased (mean: 43.1 to 77.0) and 6-min walk test distance results increased (mean: 163.6 to 252.3 m; both p < 0.0001). Conclusions In high-risk patients, TAVR for bioprosthetic aortic valve failure is associated with relatively low mortality and complication rates, improved hemodynamics, and excellent functional and quality-of-life outcomes at 1 year. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves PARTNER II; NCT01314313 )