Background The prognostic nutritional index (PNI) and Charlson comorbidity index (CCI) have been useful for predicting the prognosis based on nutritional condition and comorbidities in surgery and endoscopic mucosal dissection. The age-adjusted CCI (ACCI) has also been reported to be useful in surgery, but it has not been applied to endoscopic treatment. We therefore clarified the prognostic factors associated with ampullary tumors treated with endoscopic papillectomy (EP). Methods From January 2003 to December 2020, 236 patients who underwent EP for sporadic ampullary tumors at Nagoya University Hospital were included in this study. The 5-year survival and ability to predict the prognosis were evaluated in terms of the sex, PNI, ACCI, final pathological diagnosis, and intraductal extension. Results During a median follow-up period of 1558 days, 17 patients died. No patient died of the primary disease. The 5-year survival rate was 91.1%. In a univariate analysis, only a high ACCI (≥ 5) was extracted as a significant prognostic factor (Odds ratio, 12.2; 95% confidence interval, 3.81–39.3; p  < 0.001). The 5-year survival rates for a low ACCI (≤ 4) and high ACCI were 96.6% and 73.5%, respectively ( p  < 0.001). Conclusions A high ACCI is an important prognostic factor associated with the 5-year survival and a risk of death from other illness. Ampullary tumors suitable for EP are less likely to be a prognostic factor, and treatment-free follow-up may be acceptable in patients with a high ACCI.