Background: The impact of bile leakage (BL) on the long-term prognosis in patients with primary liver cancers after hepatectomy remains unclear. Methods: One thousand nine hundred and seventy-one consecutive patients with primary liver cancers who underwent curative hepatectomy were enrolled. 75 patients encountered BL, including 34 long-time BL (LTBL) and 41 short-time BL (STBL) according to 4-weeks demarcation. Variables associated with BL were identified using multiple logistic regression analysis. 75 patients without BL were enrolled into the Non-BL group using a one-to-one propensity score matched analysis before assessing the impact of BL on the long-term prognosis. The levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum and drain fluid were detected and compared. Results: The tumor size, type of liver cancer, operation time, blood loss and blood transfusion were independent risk factors for BL. The long-term survival showed no difference between the patients with and without BL (p > 0.05), while the LTBL was a significant predictor of poor long-term prognosis (p < 0.001). Compared with the patients without BL, the patients with BL had a higher level of IL-6 from postoperative day (POD) 1 to POD 60, and a higher level of CRP from POD 7 to POD 60. By POD 60, the levels of IL-6 and CRP hadn't restored to the normal level in the LTBL group. Conclusions: The LTBL has a negative impact on the long-term prognosis of patients with primary liver cancers after hepatectomy, in which the inflammatory responses may play a pivotal role. (C) 2019 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V.