Patients with end-stage liver disease due to chronic hepatitis B virus (HBV) infection with a persistent viral replication are generally denied liver transplantation (LT). We report the case of a patient who presented with the emergence of a YMDD escape mutant virus under lamivudine treatment, and developed terminal liver failure requiring LT. Pre-LT introduction of adefovir led to only a mild decrease in replication. The patient was treated with a combination of intravenous hepatitis B immune globulin (HBIG) that was started perioperatively, and also continued lamivudine and adefovir after LT. One year after LT, there was no evidence of HBV infection recurrence. This observation suggests that persistent high HBV replication might not be a contra-indication to LT, providing adequate and effective prophylaxis is given, using HBIG and antiviral drug combination therapy.