Objective To evaluate the value of endoscopic treatment for primary duodenal lesions. METHODS: A retrospective analysis was performed on data collected from 79 consecutive patients with primary duodenum lesions, who underwent endoscopic treatment from January 2015 to January 2018 at Beijing Friendship Hospital. Patients were divided into complication group and non-complication group, and further grouped according to lesion locations and endoscopic categories. Patient’s baseline data, endoscopic and pathological features, wound closure, the occurrence and outcome of complications were studied. RESULTS: 79 patients were enrolled and went through with endoscopic treatment, including 59 cases of endoscopic mucosal resection (EMR), 5 cases of endoscopic submucosal dissection (ESD), 6 cases of full-thickness resection with OTSC metal clips, and 9 cases of endoscopic piecemeal mucosal resection (EPMR). In all 79 cases, 8 patients (10.1%) had complications during the perioperative period, all occurred at the duodenal descending part and duodenal papilla. In all 47 cases whose lesions located at duodenal papilla and duodenal descending part, the complication rate was 17.0% (8/47). Of which, 1 patient (2.1%) had intraoperative perforation, 1 patient (2.1%) developed delayed bleeding, 6 patients (12.8%) developed mild acute pancreatitis, and all 8 patients recovered after treatment. In all the 79 patients, only 2(2.5%) cases had complications requiring further intervention with endoscopy or surgery. The complication rate at duodenal descending part and duodenal papilla (17.0%, 8/47) was significantly higher than that of non-descending and papilla part(0.0%, 0/32). The difference was statistically significant(P=0.012). In 47 patients with duodenal descending and nipple operation, the incidence of complications in the duodenoscopy group (28.0%, 7/25) was also significantly higher than that in the gastroscope group (4.5%, 1/22)（P=0.037）. Conclusion: Endoscopic treatment is safe and effective. For the operation of the duodenal descending segment and the duodenal papilla and the choice of duodenoscopy, it is necessary to be more vigilant about the occurrence of complications.