Hepatitis B virus (HBV) reinfection and recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) are associated with increased graft failure and reduced patient survival. We evaluated the effects of both HCC recurrence and HBV reinfection on the long-term survival of these patients after OLT. One hundred seventy-five patients underwent OLT for HBV-related liver diseases and were the subjects of this retrospective study. We assessed risk factors for HBV reinfection, HCC recurrence, and survival post-OLT using univariate and multivariate analyses. During a mean follow-up of 43.0 +/- 42.0 months, 88 of 175 (50.3%) patients transplanted for HBV-related liver disease had HCC prior to OLT. Thirteen (14.8%) of these patients had HCC recurrence after OLT. The mean time for recurrence of HCC was 26.1 +/- 31.9 months. Twelve of 175 (6.9%) patients developed HBV reinfection after liver transplantation. The mean time for HBV reinfection was 28.7 +/- 26.4 months. Ten of these 12 (83.3%) patients had HCC prior to OLT, and 5 (50%) developed recurrence of HCC. On multivariate analyses, pre-OLT HCC and recurrence of HCC post-OLT were significantly associated with HBV reinfection after transplantation (P = 0.031 and P < 0.001, respectively). HCC recurrence after OLT was associated with lymphovascular invasion (P < 0.001) and post-OLT chemotherapy (P < or = 0.001). The 3- and 5-year survival rates were significantly decreased in patients with HBV reinfection (P = 0.007) and in patients with HCC recurrence after OLT (P = 0.03). In conclusion, pre-OLT HCC and HCC recurrence after transplantation were associated with HBV reinfection and with decreased patient survival. Hepatitis B immunoglobulin and antiviral therapy was only partially effective in preventing HBV reinfection in patients with HCC recurrence.