Background Biliary fistula is a common but serious complication after radical resection of hilar cholangiocarcinoma. We aimed to evaluate the influencing factors of biliary fistula after radical resection, to provide insights to the clinical treatment of hilar cholangiocarcinoma. Methods Patients undergoing radical resection of hilar cholangiocarcinoma from January 1, 2015 to March 31, 2022 were selected. Patients’ personnel characteristics and laboratory test results of patients with and without biliary fistula were collected and compared. Logistic regression analyses were conducted to evaluate the associated risk factors of biliary fistula. Results 160 patients undergoing radical resection of hilar cholangiocarcinoma were included, the incidence of postoperative biliary fistulas was 20.63%. There were significant differences in the age, preoperative cholangitis and number of biliary anastomosis between biliary fistula and no biliary fistula patients (all p < 0.05). There were significant differences in the gamma glutamyl transpeptidase (GGT) on the first day after surgery, Klebsiella pneumoniae between biliary fistula and no biliary fistula patients (all p < 0.05). Logistic regression analysis indicated that age ≥ 65 years (OR  2.035, 95%CI 1.131–3.007), preoperative cholangitis (OR 1.584, 95% CI 1.081–2.361), number of biliary anastomosis ≥ 2(OR 2.866, 95%CI 1.942–3.624), GGT on the first day after surgery ≥ 120 U/L (OR 1.823, 95%CI: 1.274–2.906), preoperative bile culture for Klebsiella pneumoniae (OR 3.181, 95%CI: 2.426–3.992) were the risk factors of postoperative biliary fistulas (all p < 0.05). Conclusions There are many independent risk factors for postoperative biliary fistula in patients undergoing radical resection of hilar cholangiocarcinoma. Clinical medical workers should take early interventions and treatment measures for these high-risk patients to reduce the occurrence of postoperative biliary fistula.