Hepatitis B vaccination after liver transplantation for hepatitis B–related liver disease has been investigated as an alternative strategy to reinfection prophylaxis with hepatitis B immunoglobulin (HBIG) with conflicting results. In most studies, HBIG treatment was discontinued before vaccination. An outstanding good response was achieved with vaccination under continuous HBIG administration using hepatitis B surface antigen (HBsAg)-based vaccine containing special adjuvants. Both, adjuvants and continuous HBIG administration have been discussed as crucial factors for good response. Twenty-four patients were vaccinated with conventional double dose recombinant vaccine containing 40 μg HBsAg up to 12 times at weeks 0, 2, 4 (cycle 1), 12, 14, 16 (cycle 2), 24, 26, 28 (cycle 3), and 36, 38, 40 (cycle 4). All patients received 2,000 IU HBIG every 6 weeks (4 times intravenously and 4 times intramuscularly). A significant response was defined as reconfirmed increase of anti-HBs-antigen (anti-HBs) unexplained by HBIG administration or lack of anti-HBs decrease below 100 IU/L after discontinuation of HBIG treatment after week 48. Only 2 of 24 patients (8.3%) responded significantly. Anti-HBs started to increase after the seventh vaccination (cycle 3, during intramuscular HBIG administration) in 1 patient and after 12th vaccination (cycle 4, during intravenous HBIG administration) in the other. Maximum anti-HBs levels were >1,000 IU/L in both patients and decreased significantly slower as compared to passive prophylaxis during follow-up. In conclusion, the conventional HBsAg vaccine failed to induce a significant humoral immune response in most patients despite continued HBIG treatment. Further studies should address the question, of whether the use of potent adjuvant systems results in higher response rates. Liver Transpl 13: 367–373, 2007. © 2007 AASLD.