OBJECTIVES: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the intensive care unit (ICU). It’s associated with significant morbidity, increasing the ICU and hospital length of stay (LOS), and raising overall costs.  Literature suggests that costs could be reduced using the most efficient empiric therapy. The aim of this study was to assess the cost-effectiveness (CE) of Linezolid against generic Vancomycin as an empiric therapy for VAP patients, from the healthcare payer’s perspective.   METHODS: A decision-tree model was used to compare costs and effectiveness of Linezolid (600 mg/12 hours) and Vancomycin (1g / 12 hours) (comparator) for a cohort of patients with VAP. Effectiveness measures were: microbiological success rates, mortality rates, ICU and ward LOS and overall costs. Effectiveness and epidemiologic data were collected from published literature. Local costs (2012 US$) were obtained from Costa Rica´s Health System official databases. The model used a 12-week time horizon and only direct medical costs were considered (hospital LOS, medication costs, hematologic, gastrointestinal and skin adverse events and lab exams). Monte Carlo probabilistic sensitivity analysis (PSA) was constructed.  RESULTS:  Results showed Linezolid as more effective and less expensive option for VAP. Clinical success rate was higher with Linezolid (64.4%) against Vancomicyn, (56.1%).  Mortality was lower with linezolid (10.13% vs 15.74%).  Average ICU (and ward) LOS was 18 (9) days with Linezolid and 22 (10) days with Vancomycin.  Overall medical costs per patient were $87782.52 with Linezolid and $92771.51 with Vancomycin. CE analyses showed Linezolid is the dominant strategy. CONCLUSIONS: This is the first CE study for VAP developed in Costa Rica. Linezolid resulted as the cost-saving option for treating VAP patients in the Costa Rican clinical environment.