OBJECTIVES: Acute agitation is a transient syndrome characterized by increase in verbal and physical behavior, which results in aggression. In order to diminish the risk of damage for both, caregivers and patients, fast response drugs are required. The study is aimed to estimate the pharmacoeconomic profile of intramuscular injections of haloperidol 5mg, olanzapine 10mg and ziprasidone 20mg for acute agitation episodes associated with schizophrenia, from the perspective of a Mexican public health institution. METHODS: A discrete event simulation model was developed. The measure of effectiveness was the average time in which patients reach control ≥50%, regarding baseline level in the Overt Aggression Scales, with a time horizon of 12 hours. Clinical efficacy was extracted from published literature. A panel of experienced psychiatrists (n=12) was used to estimate the medical resource use profile. The model assesses direct medical costs (2012 US$) such as drugs, specialist’s visits, laboratory tests and management of adverse events. The results are reported in terms of ICER. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The cost per patient for ziprasidone was $693, it represents $198.6 and $64.6 less than the cost of haloperidol and olanzapine, respectively. Differences in costs were driven by less specialist’s visits with ziprasidone and high incidence of akathisia and dystonia with haloperidol. The effectiveness measure was accomplished by ziprasidone, olanzapine and haloperidol at 1.55h, 1.48h and 1.74h, respectively. Both ziprasidone and olanzapine dominated haloperidol. Results were robust to changes up to ±10% in the acquisition cost of ziprasidone. In probabilistic sensitivity analysis, results were consistent with base case, although differences between ziprasidone and olanzapine were slighter. CONCLUSIONS: In comparison to olanzapine and haloperidol, ziprasidone is associated to the lowest costs in the treatment of acute agitation episodes in schizophrenic patients in the Mexican setting, as well as better clinical performance than haloperidol.