OBJECTIVES: Ventilator – associated pneumonia (VAP) remains a significant cause of morbidity and mortality in Mexico. Development of VAP increases both the duration of intensive care unit (ICU) stay and hospitalization. The purpose of this study was to compare the cost – effectiveness ratios between four antimicrobial treatments for hospitalized adult patients with suspected or proven Gram-positive VAP due to Staphylococcus aureus in two ICUs of the Social Security Mexican Institute. METHODS: A decision tree model was developed using a Bayesian approach. The model simulated treatment of a hypothetical cohort of 1000 patients diagnosed with VAP during a time horizon of 12 weeks. Patients initiate treatment with one of four antimicrobial agents; linezolid, vancomycin, teicoplanin and imipenem. Conditional probabilities of the model were obtained from published clinical trials. Effectiveness measure was the clinical cure rate for patients with suspected or proven Staphylococcus aureus VAP. The analysis was conducted from the healthcare payer's perspective (only direct medical costs were used). Resource use and costs were obtained from hospital records and Mexican official databases. Probabilistic sensitivity analysis was performed and acceptability and health net benefits curves were constructed. RESULTS: Linezolid was associated with a shorter ICU stay and a higher clinical cure in comparison with vancomicyn, teicoplanin and imipenem (p<0.005). Linezolid showed on the 12-weeks period the lowest expected average costs per patient treated (US$38,182.9) followed by vancomicyn (US$39,345.5) and imipenem (US$42,235). Linezolid also showed the highest clinical cure rate (57.4%) followed by vancomcyin (37.2%) and teicoplanin (32.1%). Results were robust to Monte Carlo first order sensitivity analysis. CONCLUSIONS: Despite its higher cost in the Mexican market, linezolid was cost – effective for treatment of VAP. These results should be taken into account by Mexican decision makers and clinicians in the management of patients with suspected or proven Gram-positive VAP due to Staphylococcus aureus.