Preoperative serum carbohydrate antigen 125 (CA125) is used to judge the diagnosis and prognosis of various tumors. However, the relationship between preoperative serum CA125 and prognosis of hilar cholangiocarcinoma (HCCA) has not been proven. This study aims to evaluate preoperative serum CA125 in predicting the prognosis of HCCA after resection.A total of 233 patients after radical resection of HCCA were included. The associations between the levels of preoperative serum CA125 and the clinicopathological characteristics of patients were analyzed. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to identify independent risk factors associated with recurrence-free survival (RFS) and overall survival (OS).Among 233 patients, 198 (84.97%) with normal CA125 levels (≤35 U/mL) had better OS and RFS than 35 (15.02%) patients with higher CA125 levels (35 U/mL). Preoperative serum CA125 was significantly correlated with tumor size, Bismuth-Corlette classification, microvascular invasion and carcinoembryonic antigen (CEA) (p 0.001, p = 0.040, p = 0.019 and p = 0.042, respectively). The results of multivariable Cox regression showed that preoperative serum CA12535 U/mL (p = 0.002, HR = 1.910 for OS; p = 0.006, HR = 1.755 for RFS), tumor classification (p 0.001, HR = 2.110 for OS; p = 0.006, HR = 1.730 for RFS), lymph node metastasis (p 0.001, HR = 1.795 for OS; p 0.001, HR = 1.842 for RFS) and major vascular invasion (p = 0.002, HR = 1.639 for OS; p = 0.005, HR = 1.547 for RFS) were independent risk factors for both OS and RFS.Preoperative serum CA125 is a good tumor marker for predicting prognosis after radical surgery for HCCA. more...