Lamivudine prophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants. Fifty-two patients on lamivudine prophylaxis at a median of 412 days (median, 370–2040 days) after transplantation for chronic HBV-related liver disease received two courses of an accelerated schedule of double-dose recombinant HBV vaccine. Before vaccination, all patients were seronegative for HBsAg, anti-HBs and HBV DNA (by qPCR). Three intramuscular doses of vaccine (40μg each) were administered monthly and another identical course was repeated after 3 months. Lamivudine (100mg/day) was continued throughout the study. After the first course, two patients developed a weak response (anti-HBs titre of 12mIU/mL) that disappeared rapidly. One early responder developed anti-HBs (27mIU/mL) again after the second course but the other did not. Two other patients developed response (anti-HBs titre of 17 and 103mIU/mL, respectively) giving an overall response rate of 7.7%. The antibody level declined rapidly. At the end of the study, one patient who did not respond had developed viral breakthrough which was treated with adefovir dipivoxil therapy. Active immunization with two courses of double-dose recombinant HBV vaccine has limited efficacy in patients receiving lamividine prophylaxis after liver transplantation.