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Background The recommended prophylaxis against hepatitis B virus recurrence after liver transplantation based on hepatitis B immunoglobulins and lamivudine is highly expensive. A recent study reported a significant anti-HBs (antibodies against hepatitis B surface antigen) response after a reinforced vaccination against hepatitis B virus, a result not confirmed in a study from our group. Concomitant lamivudine treatment and the achievement of complete washout of anti-hepatitis B-specific immunoglobulin prior to vaccination in our study could explain the contradiction. Aims To test the efficacy of a reinforced anti-hepatitis B virus vaccination schedule without lamivudine and without previous anti-hepatitis B-specific immunoglobulin washout. Methods A double reinforced course of S-recombinant hepatitis B virus vaccination was given to seven male patients who were transplanted for hepatitis B virus-related cirrhosis. Vaccination consisted of two cycles of three intramuscular double doses (40 μg), given at month 0, 1, 2, and 3, 4, 5, respectively. The first dose was given 2 weeks after stopping lamivudine and the intravenous administration of anti-HBs immunoglobulins. The latter was continued throughout the study and follow-up period to maintain an anti-HBs titre >100 IU/L. Results At the end of both the first and the second vaccination cycle none of the patients developed an anti-HBs titre greater than the basal anti-HBs titre. Conclusion These data confirm and expand our previous data on the lack of effectiveness of conventional recombinant hepatitis B virus vaccination in liver transplant recipients.