Objective To evaluate the efficacy and safety of endoscopic papillectomy (EP) combined with endobiliary radio frequency ablation (RFA) for duodenal papilla tumor with intraductal biliary infiltration. Methods Data of 12 patients with histologically confirmed duodenal papilla tumor combined with intraductal biliary infiltration treated by EP with RFA from February 2013 to February 2019 were retrospectively analyzed. Clinical characteristics,endoscopic features, treatment efficacy and postoperative complications of patients were reviewed and recurrence was followed up. Results The median diameter of lesions measured by endoscopic ultrasound was 18.5 mm×15.5 mm, and the length of intrabiliary invasion was 14.1±5.8 mm. EP combined with RFA was successfully performed in all patients with a technical success rate of 100%. Postoperative pathology showed adenocarcinoma in 5 patients, adenoma with high-grade intraepithelial neoplasia in 6 patients, and adenoma with low-grade intraepithelial neoplasia in 1 patient. Patients received mean 4.1±1.6 times of ERCP with intraductal biopsy during a mean follow-up period of 28.5±10.4 months. Recurrence occurred in 2 patients at 14 and 20 months respectively, both were adenocarcinoma. Conclusion EP combined with RFA is effective and safe for duodenal papilla tumor with intraductal biliary infiltration. However, given the risk of recurrence, close surveillance is recommended.