OBJECTIVES:  To evaluate the cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) from the public healthcare payer perspective in Mexico. METHODS: The alternatives were prasugrel (loading dose 60 mg, maintenance dose 10 mg daily) versus clopidogrel (loading dose 300 mg, maintenance dose 75 mg daily). A Markov model was developed. Only direct medical care costs were considered for one year. The efficacy measure was a composite of the death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke and stent thrombosis reported in the trial directly comparing prasugrel and clopidogrel (TRITON TIMI-38). Three types of populations were evaluated separately; overall, patients with diabetes mellitus, and the subset of diabetics treated with insulin. Care costs were derived from medical records, and the costs of drugs were assumed to be the same. Costs and the model were validated by experts. RESULTS:  According to the model prasugrel had fewer events in the three types of populations evaluated over a 12 month time horizon. The number of events; death from cardiovascular causes, nonfatal myocardial infarction-stroke and stent thrombosis avoided by 10,000 patients were distributed as follows: overall population, 31, 650 and 147, diabetics, 92, 1363 and 203, diabetics on insulin, 174, 2531 and 499. The average cost per patient (2010 Mexican pesos) treated with prasugrel was lower compared with clopidogrel, for the overall population (MXN$ 69,972 vs. MXN$ 82,991), diabetics (MXN$79,971 vs. MXN$ 105,756) and diabetics treated with insulin (MXN$ 85,750 vs. MXN$ 137,144) CONCLUSIONS: Results from the present analysis suggest that the use of prasugrel (instead of clopidogrel) in patients with ACS undergoing PCI represents a more effective strategy at a lower cost (dominant strategy), a cost-saving alternative for institutions of public healthcare in Mexico.