Objective: Renal transplantation is recognized as the preferred approach to the management of end-stage renal disease, from both the clinical and economic perspective. In Mexico, approximately 20% of patients show acute rejection in renal transplantation (ARRT) during the first year. The purpose of this study was to estimate the cost-effectiveness of three different antibodies for the management of patients with ARRT at the Social Security Mexican Institute (IMSS). Methods: A one-year decision tree model was performed to simulate costs and health outcomes from an institutional perspective. Effectiveness measure was the rate of survival graft's rescued at the end of the follow-up period. Efficacy data and transition probabilities were taken from published literature. Comparators were horse anti-human thymocyte globulin (10mg/kg); rabbit anti-human thymocyte globulin ATG(1.5mg/kg) and Mono-OKT3(5mg). Resource use was obtained from local experts and direct costs were calculated through case-mix methodology (all unit costs were taken from official databases). The model was calibrated according to international pharmacoeconomics guidelines. One-way and probabilistic sensitivity analyses were performed using Monte Carlo Simulation second-order approach. Results: The higher effectiveness was obtained by horse-ATG (87.93%) followed by the rabbit-ATG (84.13%) and OKT3 therapy (82.13%). OKT3 therapy showed the lowest costs per patient (US$91,719) followed by horse-ATG (US$95,875) and rabbit-ATG (US$97,400). The horse-ATG showed the lowest cost per case rescued. ICERs showed that rabbit-ATG is dominated by horse-ATG and OKT3 and the horse-ATG obtained an ICER of US$75,994 vs. OKT3 (baseline). One-way analyses showed that variation in price and effects don't change these results (p<0.05). Probabilistic sensitivity analyses employing acceptability curves and component analyses showed that the horse-ATG therapy was the most cost-effective treatment. Conclusion: In Mexico, horse-ATG demonstrated to be a cost-effective polyclonal antibody for high risk patients with ARRT. These results should be taken into account by Mexican decision makers in future cost-containment policies.