It is widely agreed that hepatitis B virus immunoglobulin (HBIG) should be administered for at least 12 months to patients transplanted for hepatitis B virus (HBV)-related diseases to prevent HBV recurrence. No data are available, however, on how long this treatment should be used, and most centers currently administer HBIG on a life-long basis. Herein, we report the results of a new prophylactic strategy aiming at the discontinuation of HBIG treatment and consisting of the administration of double dose recombinant HBV vaccine (0, 1-, and 6-month schedule) to liver transplant recipients fulfilling the following criteria: (1) liver transplantation for conditions related to nonreplicative HBV infection (hepatitis B surface antigen [HBsAg] positive, hepatitis B e antigen [HBeAg] negative, and HBV DNA negative); (2) at least 18 months of HBIG administration; and (3) no HBV infection recurrence, normal or slightly altered liver graft function, and low-grade immunosuppression at the time of vaccination. Seventeen patients received HBV vaccination and 14 of them (82%) developed protective serum titers of anti-HBs (>10 IU/L). Six patients seroconverted after a first course of vaccination, whereas 8 patients required a second course (3 additional doses of vaccine). Responding patients were followed for a median of 14 months (range, 3-50) after seroconversion. During this period no HBV recurrence occurred and in only 2 patients a decrease of anti-HBs titers below 10 UI/L was observed. Our data suggest that in selected liver transplant recipients, posttransplantation HBV vaccination may be a useful and cost-effective strategy in the prophylaxis of HBV recurrence, allowing the discontinuation of life-long HBIG treatment.