Objective To study the association, clinical presentation, and diagnosis and treatment of bile duct cancer as a late complication of biliary-enteric anastomoses for benign diseases. Methods A retrospective study was carried out on 5 patients and the medical literature was reviewed. Results They were 3 males and 2 females. The average age was ( 66. 0 ± 0. 7 ) years. The average time period was ( 14. 0 ± 6. 1 ) years after biliary-enteric anastomosis. The clinical presentations included right upper quadrant pain, fever, chills and jaundice. CA19-9, CT and MRI were valuable in diagnosis. There were two patients with distal and three patients with perihilar cholangiocarcinomas (type IIIa, n=2, and type IV, n=1). Local resection with lymphadenectomy was carried out in one patient. Another patient underwent pancreaticoduodenectomy. The remaining three patients only underwent percutaneous transhepatic cholangial drainage ( PTCD). The 2 patients who underwent surgery died of progressive tumor disease at 8 and 13 months postoperatively. The other three patients who underwent palliative biliary drainage died within 6 months of PTCD. There was no significant difference between the two types of treatment ( P ＞0. 05). Conclusions Chronic cholangitis caused by reflux and bacterial infection was properly a predisposing factor leading to late development of bile duct cancer after biliary-enteric anastomosis for benign diseases. Patients treated with biliary-enteric anastomosis should be closely monitored for late development of cholangiocarcinoma. Some procedures such as choledochoduodenostomy and jejunum interposition choledochoduodenostomy should be abandoned because of their poor outcomes and severe complications. Proper indications of biliary-enteric anastomosis should strictly be followed and the Oddi's sphincter should be protected if possible to prevent late development of bile duct cancer.