The prevention of hepatitis B virus (HBV) recurrence is essential after liver transplantation in patients infected with HBV. We evaluated the efficacy of primary high-dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy in 639 HBV-infected adult patients who underwent living donor liver transplantation (LDLT) between February 1997 and December 2004. The overall 5-year survival rate was 80.7%, and recurrence of hepatocellular carcinoma was the most common cause of late mortality. Pretransplant HBV replication was observed in 392 (61.3%) patients. The interval of 10,000-IU HBIG administration to maintain antibody to hepatitis B surface antigen > 500 IU/L was 30 days in 11.4% patients, 40 to 50 days in 72.1%, and 60 days in 16.5%. At the last follow-up, 3.9% of the patients without HBV recurrence were receiving combination therapy. Overall 1-year, 3-year, 5-year, and 10-year HBV recurrence rates were 1.4%, 5.5%, 7.3%, and 8.5%, respectively. HBV recurrence occurred after a mean of 25.7 ± 16.4 months after LDLT. After HBV recurrence, 5 of 9 patients died from rapidly progressive liver failure before treatment with adefovir, and only 1 of 29 patients died after treatment with adefovir. Need for frequent HBIG infusions (≤30 days), active pretransplant HBV replication, and hepatocellular carcinoma recurrence were significant risk factors for HBV recurrence and indications for combination therapy. Our posttransplant HBV prophylaxis regimen resulted in a 5-year HBV recurrence rate of 7.3% and a mortality rate of 13.2% after HBV recurrence, showing the effectiveness of high-dose HBIG monotherapy and rescue antiviral therapy. Liver Transpl, 2008. © 2008 AASLD.