Cytomegalovirus (CMV) is an important cause of morbidity and mortality in liver transplant recipients and several different strategies of CMV chemoprophylaxis are in practice. A cost-effective analysis was performed to compare these strategies. A hypothetical cohort of liver transplant recipients was followed up for a year posttransplantation in a Markov model, as they made possible transitions to different states of health with respect to CMV infection and disease. Different strategies of chemoprophylaxis were compared. Cost per patient, yield in terms of gain in quality-adjusted stages, amount of time spent in the state of CMV disease, and CMV-related mortality were the outcome measures compared. Oral ganciclovir administered universally to all transplant recipients was the most favored strategy. Restricting prophylaxis to defined high-risk groups or extending the duration of prophylaxis beyond 3 months did not improve cost-effectiveness. The strategy of short-term, oral ganciclovir-based chemoprophylaxis for CMV in liver transplant recipients is cost-effective by current standards of healthcare interventions.