Background.The outcome of orthotopic liver transplantation (OLTX) in patients retransplanted for severe hepatitis B virus (HBV) in the first allograft has been poor due to high rates of HBV reinfection and even more aggressive disease in the second graft. Recent data suggest that hepatitis B immunoglobulin (HBIg) given after transplantation can be successful in delaying or preventing HBV reinfection in patients transplanted for chronic hepatitis B cirrhosis. We report the successful retransplantation of patients who developed recurrent or de novo hepatitis B after OLTX.Methods.Using similar HBIg regimens, two centers retransplanted seven patients after they developed recurrent or de novo hepatitis B in the first allograft. At retransplantation all seven patients were HBs antigen (Ag) positive; four patients were positive for HBeAg and HBV DNA by immunoblot assay, two patients were negative for HBeAg and HBV DNA, and one patient was positive for HBV DNA and negative for HBeAg. All patients were either HDV Ag or anti-HDV negative. One patient was anti-HCV positive. All patients received HBIg infusions after retransplantation to maintain serum anti-HBs levels >500 IU/L indefinitely.Results.After retransplantation, six of seven patients are alive (86%): all are without evidence of HBV recurrence with serum negative for HBsAg, HBeAg, and HBV DNA by immunoblot assay. Liver biopsies are normal on routine studies with immunohistochemical stains for HBcAg and HBsAg also being negative. Mean follow-up of these six patients is 40.1 months (range 21-63 months). One patient (14%) developed HBV reinfection 7 months after his second transplant, in spite of maintaining target anti-HBs levels. He maintained stable liver function with minimal evidence of clinical hepatitis B, but died 8 months later from an unrelated stroke.Conclusions.We conclude that patients with recurrent or de novo hepatitis B after OLTX can be successfully retransplanted using aggressive immunoprophylaxis to prevent HBV reinfection. The failure of HBIg therapy in one patient underscores the need for other effective adjunctive anti-HBV modalities.