Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation. We investigated the efficacy of a reinforced triple course of HBV vaccination in 17 patients transplanted for HBsAg—positive cirrhosis 2 to 7 years earlier. The first cycle consisted of 3 double intramuscular doses (40 μg) of recombinant vaccine at month 0, 1, and 2, respectively. This was followed, in nonresponders, by a second cycle of 6 intradermal 10 μg doses every 15 days. All nonresponders then received a third cycle identical to the first one. Vaccination started 4.5 months after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. All patients were seronegative for HBsAg and HBV-DNA (by PCR) and positive for anti-HBe, and 7 were positive for anti-HDV. After the first cycle one patient (#5, 53 years old, male) developed an anti-HBs titer of 154 IU/L, another (#12) reached a titer of 20 IU/L and the remainder had titers <10 IU/L. At month 7, patient #5 reached a titer of 687 IU/L. After the second cycle only one additional patient (#9) had a slight response (an anti-HBs titer of 37 IU/L). After the third cycle patient #9 rose to an anti-HBs titer of 280 IU/L, patient #12 dropped to 10 IU/L, and no other patient responded. In conclusion, a highly reinforced HBV vaccination program is effective only in a few patients who had liver transplants for HBV—related cirrhosis.