Objective To evaluate the clinical efficacy of endoscopy for early cancer of duodenal papilla. Methods A retrospective analysis was performed on data collected from 23 consecutive patients with early cancer of duodenal papilla, who underwent endoscopic treatment from January 2015 to January 2021 in Beijing Friendship Hospital. Baseline data, endoscopic and pathological data, occurrence and outcome of complications were studied. Results Twenty-three patients successfully received endoscopic treatment. The maximal diameter of lesions evaluated under endoscopy was 1.90±0.83 cm. Among the 23 cases, 20 underwent endoscopic mucosal resection and 3 underwent endoscopic piecemeal mucosal resection. Delayed bleeding occurred in 5 cases (21.7%), 3 patients (13.0%) developed postoperative hyperamylasemia, 6 patients (26.1%) developed mild acute pancreatitis, and 1 patient (4.3%) had pancreatic duct stent displacement after the operation, which improved after medical or endoscopic treatment. No perforation occurred during the perioperative period. In terms of final pathology, the en bloc resection rate was 82.6% (19/23), and the complete resection rate was 78.3% (18/23). Preoperative endoscopic ultrasonography showed that 19 lesions were confined to the mucosal layer, which were all demonstrated by postoperative pathology. Four other cases were suspected to be involved in the submucosa or the end of the pancreaticobiliary duct under endoscopic ultrasonography, two of which were confined to the mucosal layer, and the other 2 cases involved the submucosal layer, so additional surgery was performed. A total of 18 patients were followed up, among whom 14 achieved complete resection of postoperative pathology, and 2 patients (14.3%, 2/14) were found to have recurrence at 12 and 51 months respectively after the treatment and did not relapse after surgical treatment and endoscopic treatment respectively. Among 4 other patients of follow-up whose pathology did not achieve complete resection, 1 had no recurrence, and the other 3 received additional surgical treatment without recurrence. Conclusion Endoscopic treatment for early cancer of duodenal papilla is safe and effective. It is necessary to improve preoperative evaluation, stay alert to perioperative complications, and pay attention to regular postoperative endoscopic follow-up.