AIM: To analyze the prognostic factors influencing the overall survival of peripheral cholangiocarcinoma (PCC)patients undergoing surgical treatment during 25 years at a single institution.METHODS: This study retrospectively reviewed prospectively collecting data about 373 patients with histologically proven PCC who underwent surgical treatment between 1977 and 2001.RESULTS: Three hundred and seventy-three PCC patients (159 men and 214 women) underwent surgical treatment from 1977 to 2001. Among them, 187 PCC patients underwent hepatectomy and 135 had curative resection (curative resectability rate: 36.2%). The follow-up duration ranged from 1.05 to 167.6 mo (mean/median = 14.1/7.2 mo).Overall cumulative survival rates at 1, 3, and 5 years were 32.5%, 9.2%, and 4.1%, respectively. Univariate log-rank analysis identified the following as adverse influences on overall survival: presence of symptoms, absence of mucobilia, elevated CEA and CA 19-9 levels, non-papillary tumor type, receiving non-hepatectomy, advanced tumor staging, lack of post-operative chemotherapy, and radiotherapy. Meanwhile, multivariate Coxs proportional hazard analysis demonstrated that absence of mucobilia,non-papillary tumor type, advanced tumor staging, nonhepatectomy, and lack of post-operative chemotherapy were the five independent prognostic factors that adversely affected overall survival.CONCLUSION: Favorable overall survival of PCC patients undergoing surgical treatment depends on early tumor stage, presence of mucobilia, papillary tumor type, hepatic resection, and post-operative chemotherapy.