Background and Aims Large sporadic duodenal adenomas are uncommon but they harbor malignant potential, which requires consideration of definitive treatment. EMR is gaining acceptance as an effective and safe alternative to high-risk surgical procedures, but data on long-term outcomes are limited. Herein we describe the short- and long-term outcomes of these lesions in a tertiary referral center. Methods Prospectively collected data were analyzed to identify risk factors for adverse events and outcomes. Patient demographics, lesion characteristics, and procedural technical data were collected. Results From 2007 to 2015, 106 adenomas ≥10 mm were resected (mean patient age, 69 years; 54% male; median size, 25 mm; interquartile range [IQR], 19–40). Complete endoscopic resection was achieved in 96%. Intraprocedural bleeding occurred in 43% of cases and was associated with lesion size (P <.001), number of resected specimens (P =.003), and longer procedures (P =.001). Delayed bleeding occurred in 15% (56% did not require active intervention) and was associated with lesion size (P =.03). Perforation occurred in 3 patients. The 30-day mortality was 0%. Median follow-up was 22 months (IQR, 7–45). Histologically proven adenoma recurrence was identified and treated in 12 of 83 patients (14.4%) on first surveillance endoscopy. For the 53 patients for whom follow-up ≥12 months was available (median follow-up, 36 months; IQR, 24–51), 48 patients (90.6%) were free of adenoma and considered cured. Conclusions In a tertiary referral center, endoscopic resection of duodenal adenomas is a safe and effective alternative to surgery. Lesion size is strongly associated with adverse events, particularly intraprocedural bleeding and delayed bleeding. Good long-term outcomes are demonstrated.