Background: - The safety and efficacy of transcatheter aortic valve replacement (TAVR) in patients who have severe aortic stenosis and aortic annuli larger than that specified in manufacturer guidelines and who have been rejected for surgery is unknown. Methods: All patients who underwent TAVR with a 34-mm Evolut valve (Medtronic, Minneapolis, Minn.) at a single center from 2016-2022 were included. The cohort (n=530) was divided into an off-label group (cases, n=36), defined by an aortic annulus perimeter above the manufacturer’s recommended range for the 34-mm Evolut valve (>94.2 mm), and an on-label group (controls, n=494). All patients in the off-label group were deemed prohibitive surgical risk and were declined for surgical aortic valve replacement by the Heart Team. All patients were followed for the clinical outcomes of in-hospital mortality, permanent pacemaker (PPM) implantation, aortic valve reintervention, device migration, and paravalvular leak (PVL). Results: Cases had a statistically significant larger annular perimeter than controls (97.2 vs 84.7 mm; P<0.0001). Most cases (88.9%) and controls (98.6%) had mild or no PVL, and 94.4% of cases survived in-hospital. Cases had higher rates of moderate/severe PVL (11.1% vs 1.4%, P≤0.0001), device migration (5.6% vs 0.3%, P≤0.0001), and in-hospital mortality (5.6% vs 0.8%, P=0.0094) reflecting the increased anatomic and procedural risk associated with extreme annular enlargement, but similar incidences of aortic valve reintervention (0.4% vs 0%, P=0.70) and PPM (8.3% vs 13.2%, P=0.37).  Conclusions: Self-expanding TAVR valves can be used safely and effectively to treat patients with an oversized aortic annulus who are rejected for surgical intervention. The findings of this study can help guide management in these patients who lack alternatives.