The presence of a positive hepatitis B surface antigen (HBsAg) has been considered a highly questionable indication for orthotopic liver transplantation. We report our experience in the treatment of HBsAg-positive HBV-DNA-negative cirrhotics with liver transplantation, whether or not followed by passive prophylaxis with specific immunoglobulins. Of the 123 cirrhotics who received transplants at our institution since May 1986, 39 (31.7%) were HBsAg positive; of these, 1 was HBV-DNA positive, and 4 were hepatitis Be antigen (HBeAg) positive. Since April 1991, 25 HBsAg-positive HBV-DNA-negative cirrhotics have undergone an original protocol with the periodical intramuscular administration of 5,000 IU of specific immunoglobulins starting in the anhepatic phase and lasting for at least 1 year. There were no differences among cirrhotics in terms of operative mortality and long-term survival with respect to the presence of the HBsAg. Of the 35 HBsAg-positive HBV-DNA-negative patients having a follow-up of 1 month or longer, 12 (34.3%) developed HBsAg recurrence; of them, 4 (33.3%) had received a complete prophylaxis, whereas 8 (66.7%) had not. The recurrence rate was 80% (8 out of 10) in the group of patients who had not received the prophylaxis and 16% (4 out of 25) in the group who had received the prophylaxis (P = .0003). The actuarial recurrence rate in the treated patients was 20.2% and 20.2% after 1 and 3 years, respectively, whereas in the untreated group it was 60.0% and 70.0% (P < .01). The hazard of recurrence of treated patients was reduced to 24.9% compared with untreated patients. Liver transplantation can be performed in HBsAg-positive HBV DNA negative patients without an increase in the operative risk or a worsening of long-term results. Immunoglobulin prophylaxis seems to be effective in preventing hepatitis recurrence after transplantation.