Background and Aims Bile leakage is a common complication after hepatectomy, which will cause prolonged hospital stay and delayed removal of the abdominal drainage tube, thereby increasing the suffering and economic costs of patients. Severe bile leakage can lead to abdominal infection, sepsis, and even death. This study aims to investigate the factors associated with postoperative bile leakage through retrospective analysis to reduce the incidence of postoperative bile leakage in clinical practice.Methods The general information and clinical data of patients undergoing hepatectomy in Xiangya Hospital of Central South University from January 1, 2020 to October 1, 2022 were collected retrospectively. The influencing factors for postoperative bile leakage were determined by univariate and multivariate Logistic analyses.Results A total of 1 845 patients who underwent hepatectomy were finally included. Of the patients, bile leakage occurred in 59 cases (3.2%), which was classified as grade A in 36 cases, grade B in 20 cases and grade C in 3 cases. The results of univariate analysis indicated that previous history of hepatectomy (χ²=9.337, P=0.002), diagnosis of malignant tumor (χ²=10.849, P=0.001), anatomical hepatectomy (χ²=8.015, P=0.005), operative time (t=4.613, P<0.001), blood loss (t=4.274, P<0.001), blood transfusion or not (χ²=5.129, P=0.024) and the use of fibrin glue (χ²=10.289, P=0.001) were related to postoperative bile leakage. The results of Logistic analysis showed that previous history of hepatectomy was an independent risk factor (P=0.003), while anatomical hepatectomy (P=0.006) and the use of fibrin glue during the operation (P=0.002) were independent protective factors for postoperative bile leakage. Conversion therapy was associated with postoperative bile leakage in patients with primary liver cancer (χ²=74.594, P<0.001), and only transcatheter arterial chemoembolization (TACE), among the local treatments, was an independent risk factor for postoperative bile leakage (P<0.001).Conclusion For patients with a previous history of hepatectomy or who have received conversion therapy, mainly containing TACE, preoperative planning is essential, and more caution should be taken during the operation. Anatomical hepatectomy and intraoperative use of fibrin glue can help reduce the occurrence of bile leakage.