Objective: To evaluate the clinicopathologic features and prognosis of ampullary adenocarcinoma (AA). Methods: The proportion of AA in patients who underwent pancreaticoduodenectomy were calculated in Ruijin hospital from January 2017 to December 2019. The clinical data and pathological features were analyzed. According to the new histological classification standard in the fifth edition of the World Health Organization classification of digestive system tumors in 2019, AA was reclassified and the risk factors for poor prognosis were analyzed. Results: It revealed that AA account for 6.95%(101/1454) in patients undergone pancreaticoduodenectomies. The median age of onset was 64 years, and the male to female ratio was 46∶55. The proportion of histological sub-types were 19.80%(20/101) for intestinal-type adenocarcinoma, 43.56% (44/101) for pancreatobiliary-type adenocarcinoma and 36.63% (37/101) for tubular adenocarcinoma. Among these 101 patients, 26 patients were lost to follow-up, and the remaining 75 patients were followed up for 1-45 months, with a median postoperative follow-up period of 18 months. The 1-year survival rate of the patients was 78.58%, and the 2-year survival rate was 67.40%. Log-rank survival analysis showed difference in overall survival between the non-intestinal-type adenocarcinoma group (pancreaticobiliary-type adenocarcinoma and tubular adenocarcinoma) and the intestinal-type adenocarcinoma group (P=0.0415). There was also statistical difference in the overall survival between the CK7 positive group and the CK7 negative group of tumor cells (P=0.0425). Conclusions: AA occurres frequently in the elderly and there is no significant gender difference. Pancreatobiliary-type carcinoma and tubular adenocarcinoma are dominant histological types, and intestinal-type adenocarcinoma accounts for only a small portion. Non intestinal-type adenocarcinoma and CK7 positivity are risk factors for poor prognosis of AA.