OBJECTIVES: Immunosuppressive agents have affected the incidence of acute rejection and early graft survival. The purpose of this study was to evaluate the cost-utility of sirolimus versus tacrolimus for primary prevention of graft rejection in renal transplant recipients using the Mexican Institute of Social Security (IMSS) perspective. METHODS: A Markov model was developed to estimate the cost-effectiveness of sirolimus versus tacrolimus to prevent graft rejection in adult patients with end-stage renal disease (ESRD). The model estimates total costs and QALYs per patient in each prophylaxis group. To extrapolate trial results to lifetime horizon, the model was extended through one-year Markov cycles. The probabilities of experiencing a graft loss, dialysis, and death were estimated from trial published data; long-term mortality, acquisition costs, and direct treatment costs were retrieved using IMSS published sources. Cost utility assessment was expressed in terms of cost per QALY gained. All costs are presented in 2011 US dollars. Probabilistic sensitivity analyses were carried out to test the robustness of the results. RESULTS: In comparison to tracolimus, sirolimus improved life expectancy, number of QALYs gained, and reduced incidence of complications. The lifetime overall costs of prevent graft rejection in adult patients with ESRD resulted in a cost per QALY gained of