Hepatitis B virus (HBV) infection is the leading cause of cirrhosis worldwide. One effective strategy to prevent recurrence or transmission of HBV infection after liver transplantation exists is prescription of Lamivudine, although it is associated with high resistance rates. Adefovir dipivoxil (AD) is a nucleotide analogue of adenosine that has achieved significant results in virologic, biochemical, and clinical parameters in lamivudine-resistant HBV-infected patients. Between 1990 and 2003 7 adult recipients of orthotopic liver transplants who experienced lamivudine-resistant HBV infection (pretransplantation or posttransplantation) were enrolled in a prospective study to administer AD for 48 weeks. At baseline they showed serum HBV DNA between 2.2 x 10(6) and 1.1 x 10(8) copies/mL. After 48 weeks of AD treatment, the median time-weighted average change in serum HBV DNA (log 10 copies/mL) was -3.19 (SD, 1.65). In 3 patients with HBV, DNA was undetectable (<400 copies/mL) at the end of the follow-up. HBe antigen seroconversion was observed in 1 patient. No significant adverse effects were recorded, except for renal functional impairment in 1 patient who had previous renal insufficiency. In our study, adefovir was an effective drug to suppression HBV replication in liver transplant recipients with lamivudine-resistant HBV. Excluding renal function abnormalities, tolerance of the drug was excellent. None of the patients developed resistance to adefovir. Therapy with AD in liver transplant recipients is effective and safe, although renal function should be monitored closely.