OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) is an infection associated with high health expenditure for the Portuguese National Health Service (NHS). A decision analytic model was adapted to the Portuguese setting to evaluate the cost-effectiveness (CEA) of linezolid vs.vancomycin in MRSA cSSTI. METHODS: Published Bayesian evidence synthesis results were used to populate efficacy parameters of the model. Resource utilization and MRSA prevalence rates were obtained through an expert panel of Portuguese clinicians and costs from published sources were applied to resource units. Analyses were done from the Portuguese NHS perspective. Both univariate and probabilistic sensitivity analyses were performed to test the robustness of model results. RESULTS: Average cost per patient for linezolid and vancomycin treatments were 15,195€ and 17,345€ respectively. Average effectiveness gained with linezolid treatment was 0.002QALYs. Average saving obtained with linezolid treatment was 2150€ per patient. CONCLUSIONS: Linezolid is a dominant strategy compared to vancomycin: less costly and more effective. Compared to vancomycin, linezolid is expected to result in lower total costs that offset its higher acquisition cost in cSSTI in Portugal.