Background Few reports have evaluated the efficacy of re-operation for relapse after initial surgery for hepatocellular carcinoma (HCC) with bile duct thrombosis (BDT).The aim of this study was to investigate the efficacy of initial surgery and subsequent re-operation for HCC with BDT, and their effects on prognosis.Methods The clinical data of 880 patients with HCC, including 28 patients with BDT, who underwent radical hepatectomy between 1998 and 2008 in our hospital, were reviewed.The effects of BDT and re-operation on prognosis were retrospectively analyzed.Results The 1-, 3- and 5-year survival rates were 89.3%, 46.4% and 21.4%, respectively, in 28 patients with BDT versus 91.4%, 52.9% and 20.9% in 852 patients without BDT (P ＞0.05).Six patients with BDT underwent re-operation after disease relapse, and their survival time was significantly longer than those who did not undergo re-operation (P ＜0.05).Multivariate analysis indicated that portal vein invasion and tumor size were independently associated with tumor relapse and prognosis (P＜0.05).Univariate analysis and multivariate analyses showed that obstructive jaundice was not significantly correlated with tumor relapse or prognosis (P ＞0.05).Conclusions Hepatectomy plus BDT removal is an effective treatment option for HCC with BDT.Obstructive jaundice is not a contraindication for surgery.Re-operation after relapse can provide good outcomes if the cases are appropriately selected.