Objective: Cytomegalovirus (CMV) immune globulin (CMVIG) has been shown to significantly reduce severe CMV-associated disease complicating orthotopic liver transplant (OLT). We evaluated the economic impact of severe CMV-associated disease and calculated the marginal cost-effectiveness (C/E) of routine prophylaxis with CMVIG after OLT.Design: C/E analysis.Setting: Four teaching hospitals in Boston.Patients: Patients who underwent OLT from January 1988 through June 1990.Measurements: We gathered actual cost data of hospital care for patients enrolled in a clinical trial of CMVIG prophylaxis in OLT. We calculated average outpatient expenses from a separate group of patients undergoing OLT and developed a regression model to estimate costs during the first year post-transplant (R2=0.77). Based on this model, we calculated variable costs (in 1999 US dollars) for all patients in the randomized trial. From the published literature we obtained the probability of CMV outcomes and of long-term survival after OLT. We then developed a decision analytical model to determine an incremental C/E ratio, using a Markov simulation to estimate long-term survival and long-term costs. We discounted costs and life-years at 3% and 5% per yr.Results: Based on the efficacy rate of 54% in the controlled trial, we estimate that CMVIG will increase life expectancy by 0.65 discounted years at an additional cost of $11 600, providing a marginal C/E ratio of $17 900/yr life saved. Examining the confidence limits of efficacy, we estimate that CMVIG will have a marginal C/E ratio of $66 200 gained/yr at an efficacy of 11% and $14 000 gained/yr at an efficacy of 83%.Conclusion: After OLT, prophylactic CMVIG has an incremental C/E ratio comparable to that of other well-accepted medical therapies and should be used routinely in these patients.