To study the clinical effect of non-ampullary duodenal mucosal lesions treated by endoscopic resection. A retrospective analysis was performed on the data of 58 cases of duodenal non-ampullary mucosal lesions treated by endoscopic resection from January 2016 to June 2019 from 3 hospitals. Among 58 cases, 27 lesions (46.6%) were located in the duodenal bulb and 31 (53.4%) in the duodenal descending part (including the ball-drop boundary). Forty-six patients (79.3%) received endoscopic mucosal resection, 7 (12.1%) received endoscopic submucosal dissection and 5 (8.6%) received pre-cut endoscopic mucosal resection. Few postoperative complications were found except for 1 case of intraoperative bleeding, 1 case of delayed bleeding 2 days after surgery, 1 case of lesion residual and 2 cases of postoperative abdominal pain. No perforation occurred. Endoscopic treatment of non-ampullary duodenal mucosal lesions is safe and effective.