Background.We conducted a trial of long-term ganciclovir prophylaxis for prevention of primary cytomegalovirus (CMV) disease in CMV-seronegative liver transplant recipients with CMV-seropositive donors.Methods.Patients received intravenous ganciclovir at a dose of 6 mg/kg once a day from day 1 to day 30 after transplant, and then at a dose of 6 mg/kg once a day, Monday through Friday, until day 100. Fortyseven consecutive patients were evaluated. Due to the primary physician's decision or administrative error, 10 patients received less than 7 weeks of ganciclovir(mean duration, 3 weeks).Results.Four of the 10 (40%) patients who received less than 7 weeks of ganciclovir developed CMV disease (hepatitis). In contrast, none of the 37 patients given 100 days of prophylactic ganciclovir developed CMV disease while receiving ganciclovir. Two patients (5.4%) subsequently developed CMV disease (hepatitis) 21 and 88 days, respectively, after completing their ganciclovir prophylaxis. Reversible neutropenia in three patients (8.1%) was the only side effect associated with long-term ganciclovir. Complications from central intravenous catheters did not occur.Conclusions.These results reaffirm the efficacy and safety of long-term ganciclovir prophylaxis for prevention of primary CMV disease in a large number of high-risk CMV-seronegative liver transplant recipients with CMV-seropositive donors.