Objective To evaluate the clinical efficacy of endoscopic treatment of superficial non-ampullary duodenal adenoma. Methods The clinical data and follow-up information of patients diagnosed with superficial non-ampullary duodenal adenoma and treated endoscopically in Peking University First Hospital from January 2013 to January 2024 were retrospectively analyzed, and the operation time, complications, en bloc resection rate and complete resection rate of different endoscopic treatment methods were studied. Results A total of 86 patients were included in this study. Treatment modalities included endoscopic mucosal resection (EMR) in 46 cases, endoscopic submucosal dissection (EMR), 16 cases (ESD) and 24 cases (ESD with Snare (ESD-S). Of the 86 cases, 71 were pathologically diagnosed as low-grade adenomas and 15 were pathologically diagnosed as high-grade adenomas or intramucosal adenocarcinoma. The operation time of the three groups was significantly different. No delayed bleeding occurred in perioperative period, 2 patients had intraoperative perforation, which was recovered by conservative treatment, 4 patients had delayed perforation, of which 3 patients were recovered by surgical treatment, and 1 patient was recovered by conservative treatment. The en bloc resection rates of EMR, ESD-S and ESD groups were 80.4%, 91.7% and 100%, and the complete resection rates were 80.4%, 91.7% and 93.8%, respectively. During the follow-up period, 2 patients had local recurrence, but no recurrence occurred after follow-up endoscopic therapy. Conclusion Endoscopic treatment of superficial non-ampullary duodenal adenoma is safe and effective. In addition to traditional EMR and ESD, modified ESD is also an effective procedure for endoscopic treatment of non-ampullary duodenal adenoma. Timely identification of perforation, accurate wound closure and effective drainage of digestive fluid during the operation can reduce the risk of conversion to surgery. It is feasible and effective for patients with recurrence to receive endoscopic therapy again.