IMPORTANCE Transcatheter aortic valve replacement (TAVR) was approved by the US Food and Drug Administration for severe aortic stenosis in patients who cannot undergo surgery and for patients at high operative risk. Use of TAVR for off-label indications has not been previously reported. OBJECTIVE To evaluate patterns and adverse outcomes of off-label use of TAVR in US clinical practice. DESIGN, SETTING AND PARTICIPANTS Patients receiving commercially funded TAVR in the United States are included in the Transcatheter Valve Therapy Registry. A total of 23 847 patients from 328 sites performing TAVR between November 9, 2011, and September 30 2014, were assessed for this study. Off-label TAVR was defined as TAVR in patients with known bicuspid valve, moderate aortic stenosis, severe mitral regurgitation, severe aortic regurgitation, or subaortic stenosis. Data were linked with the Centers for Medicare and Medicaid Services for 15 397 patients to evaluate 30-day and 1-year outcomes. EXPOSURE Off-label use of TAVR. MAIN OUTCOMES AND MEASURES Frequency of off-label TAVR use and the association with in-hospital, 30-day, and 1-year adverse outcomes. RESULTS Among the 23 847 patients in the study (11 876 women and 11 971 men; median age 84 years [interquartile range, 78-88 years]), off-label TAVR was used in 2272 patients (9.5%). In-hospital mortality was higher among patients receiving off-label TAVR than those receiving on-label TAVR (6.3%vs 4.7%; P < .001), as was 30-day mortality (8.5%vs 6.1%; P < .001) and 1-year mortality (25.6%vs 22.1%; P = .001). Adjusted 30-day mortality was higher in the off-label group (hazard ratio, 1.27; 95%CI, 1.04-1.55; P = .02), while adjusted 1-year mortality was similar in the 2 groups (hazard ratio, 1.11; 95%CI, 0.98-1.25; P = .11). The median rate of off-label TAVR use per hospital was 6.8%(range, 0%-34.7%; interquartile range, 3.4%-12.1%) with hospitals in the highest tertile of off-label use associated with increased 30-day adverse cardiovascular events compared with the lowest tertile. However, this difference was not observed in adjusted 30-day or 1-year outcomes. CONCLUSIONS AND RELEVANCE Approximately 1 in 10 patients in the United States have received TAVR for an off-label indication. After adjustment, 1-year mortality was similar in these patients to that in patients who received TAVR for an on-label indication. These results reinforce the need for additional research on the efficacy of off-label TAVR use.