Objective To explore the etiologies of persistent hyperbilirubinemia in follow-up patients after liver transplantation. Methods The clinical data of 527 follow-up patients after liver transplantation at the department of hepatobiliary surgery in Peking University People's Hospital between May 2000 and Dec 2009 were analyzed retrospectively. Results Sixty-five patients experienced persistent hyperbilirubinemia,there were 34 cases of biliary complications (52.3％ ),14 cases with drug-induced liver injury(21.5％ ),6 cases with hepatitis B or C recurrence(9.2％ ),4 cases with acute rejection (6.2％ ) 3 cases with inflammatory stenosis of the duodenal papilla ( 4.6％ ),2 cases with hepatic carcinoma recurrence(3.1％ ),1 case with neomalignancy and 1 case with unknown reason.Treatment included use of liver protectant and choleretics,the adjustment and replacement of anti-rejection drugs,cholelithotomy by choledochoscope,PTCD,placement of biliary stent and re-operation.Of all the 65 cases 50 patients were cured or in stable condition,15 patients died. Conclusions Jaundice is a common clinical manifestation after liver transplantation with multiple and complicated causes.Diffuse stricture of intrahepatic biliary tract predicts poor prognosis,drug-related liver injury was less common cause of hyperbilirubinemia and often misdiagnosed.