Endoscopic submucosal dissection (ESD) in the duodenal bulb is technically challenging because of the thin wall and perpendicular angulation of the duodenum. However, ESD allows for the en bloc resection of both mucosal and submucosal lesions, which may theoretically allow for lower recurrence rates. We present 2 cases of ESD for resection of submucosal neoplasms in the duodenal bulb, and we highlight techniques and strategies for successful resection (Video 1, available online at www.VideoGIE.org ).