Recurrent hepatitis B virus (HBV) infection of the liver graft is characterized by a severe outcome and high level of HBV replication. For many investigators, retransplantation appears contraindicated because of constant recurrence and a high mortality. We report our experience in this setting. Between January 1985 and December 1995, 10 patients who underwent retransplantation for HBV graft reinfection were studied. According to the antiviral treatment administered after HBV recurrence on the first liver graft and the protocol of antiviral prophylaxis after retransplantation, two groups were defined: group 1 underwent retransplantation before January 1992 (n ؍ 5), and group 2 underwent retransplantation after January 1992 (n ؍ 5). At the time of reinfection, serum HBV DNA was positive in all patients, hepatitis Be antigen (HBeAg) was positive in 6 patients. Antiviral therapy was administered to 7 patients (group 1, adenine arabinoside mono phosphate [ara-Amp; n ؍ 3]; group 2, ara-Amp [n ؍ 5], ganciclovir [n ؍ 4]). After retransplanta-tion, long-term antibody to HB surface antigen (anti-HBs) immunoglobulins were administered to achieve an anti-HBs titer greater than 100 IU/L in group 1 and to achieve an anti-HBs titer greater than 500 IU/L associated with prophylactic intravenous ganciclovir administration (5 mg/kg three times weekly) for 2 years in group 2. In group 1, all patients died, either perioperatively or secondary to HBV recurrence (1 year survival, 0%). In group 2, 1 patient died 50 months after retransplantation of HBV cirrhosis on the second graft, and 4 patients remained HBsAg negative at a mean of 41 months (range, 24 to 68 months) after retransplantation. The prognosis of retransplantation for HBV recurrence was dramatically improved by the administration of antiviral therapy before retransplantation and the maintenance of a high anti-HBs level combined with antiviral therapy after retransplantation.