Objective To explore the long‑term effect of endoscopic radiofrequency ablation for the treatment of unresectable ampullary carcinoma. Methods Clinical data of patients with ampullary carcinoma who received endoscopic radiofrequency ablation in the Third Affiliated Hospital of Naval Medical University from January 2012 to May 2019 were retrospectively collected, including basic information, frequency of radiofrequency ablation, the type of biliary stent, postoperative complications, and follow‑up. Kaplan‑Meier method was used to analyze the survival of patients after endoscopic radiofrequency ablation. Relationship between frequency of radiofrequency ablation, type of biliary stent and overall survival time was analyzed. Results A total of 50 patients were enrolled, including 31 males and 19 females, aged 73.0±9.7 years. Twenty‑five patients (50.0%) underwent 1 radiofrequency ablation treatment, while 25 patients (50.0%) underwent radiofrequency ablation treatments more than twice. Postoperative complications occurred in 6 patients (12.0%), all of which were mild symptoms. The average follow‑up was 22.3 months, with a total of 39 (78.0%) deaths, 5 (10.0%) lost to follow‑up, and 6 (12.0%) surviving. The median overall survival time was 16.9 (95%CI: 9.1‑24.8) months, with cumulative survival rates of 62.0%, 38.5%, 27.0%, and 12.6% at 1, 2, 3, and 5 years, respectively. The median overall survival time of those treated with radiofrequency ablation ≥2 times showed a trend of prolongation compared to patients treated once, but the difference was not statistically significant [26.7 (95%CI: 9.7‑43.7) months VS 12.6 (95%CI: 4.9‑20.3) months, χ2=3.049, P=0.081]. Plastic stents were used in 32 patients (64.0%) and metal stents in 18 patients (36.0%). There was no significant difference in median overall survival time between patients using metal and plastic stents [17.1 (95%CI: 6.1-28.0) months VS 15.9 (95%CI: 6.9-24.9) months，χ2=0.029，P=0.865]. Conclusion Endoscopic radiofrequency ablation is a safe treatment for unresectable ampullary carcinoma, and multiple consecutive treatments may increase the survival benefit.