Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection is associated with a high rate of graft loss and poor survival, unless re-infection can be prevented. Human hepatitis B immune globulin (HBIG) has long been utilized to prevent re-infection. More recently, an anti-viral agent has been utilized along with HBIG. However, the regimens utilized have varied considerably among LT programmes and the optimal regimen has never been defined. We conducted a retrospective analysis of 41 patients who underwent LT for HBV at our centre since 1985 and received either HBIG with or without an anti-viral agent. The mean age of these patients was 46 years; 81% were male and 88% white. The mean and maximal follow-up were 5.9 and 15 years respectively. Eight out of 15 E-antigen-positive patients who received HBIG alone developed recurrence after a mean of 17 months. In contrast, none of 10 E-Ag-negative patients who received HBIG alone and none of the 10 E-antigen-positive patients who received both HBIG and either lamivudine or adefovir developed recurrence. As long as the anti-HB surface remained detectable, no absolute minimum serum level appeared to lead to recurrent HBV. We concluded that recurrence of HBV following LT can be prevented in E-antigen-positive patients with a combination of HBIG and an anti-viral agent. In contrast, recurrence can be prevented in E-antigen-negative patients with HBIG alone. Maintaining a serum anti-HB surface level above a minimum arbitrary titre of 200 pg/mL did not appear to be necessary for effective HBIG prophylaxis.