For the prevention of recurrent hepatitis B virus (HBV) infection after liver transplantation (LT), the efficacy of hepatitis B immunoglobulin (HBIg) has been largely demonstrated. The aim of this pilot study was to determine if the addition of lamivudine to HBIg in the prevention of HBV recurrence after LT could be more effective. Sixty HBsAg-positive/HBV DNA-negative patients underwent LT from October 1990 to December 2001. All 60 patients received intravenous HBIg to maintain serum anti-HB levels above 500 IU/L, indefinitely. Since 1997, 17 patients have received combined oral lamivudine (150 mg/day) and HBIg, and were compared with the historical cohort of 43 patients. In the historical control group, the recurrence rate was 10/43 (23%) after a 98-month median follow-up. Five patients died from HBV-related liver disease. After a 30-month median follow-up, none of the 17 patients in the combined prophylaxis group experienced HBV recurrence, and HBV DNA was undetectable by PCR in at least three serum samples per patient. HBV recurrence was significantly lower when compared with the historical control group (10/43 vs. 0/17, p < 0.01). Our results suggest that combined lamivudine and HBIg can avoid the recurrence of HBV infection in patients who are HBsAg-positive/HBV DNA negative before LT.