OBJECTIVES: Seventy-nine percent of the skin and soft tissue infections (SSTI) are caused by staphylococcus aureus, from which 1/3 is methicilin-resistant staphylococcus aureus (MRSA). This study aims to compare SSTI-MRSA treatment costs with linezolid versus branded and generic vancomycin under the Brazilian public payer perspective. METHODS: A cost comparison study was performed to compare linezolid versus generic and branded vancomycin. As supported by clinical studies, overall treatment duration of 15 days with linezolid and 14 days with vancomycin was considered, using PO linezolid after a minimum 4-days cycle of IV infusion while vancomycin (1g bid) was entirely IV. A decision-tree model simulated SSTI-MRSA treatment assuming linezolid (600mg bid) IV can be switched to PO after 4-days and patients can be discharged if PO is implemented at physician discretion. Length of stay (LOS) and IV linezolid duration were ranged in one-way sensitivity analysis. Only direct medical costs were included in the analysis (hospital charges, medical visits, medical supplies and drug acquisition costs) and unit costs were obtained from Brazilian official price lists (2010 USD values). RESULTS: The linezolid scheme with 4-days IV (LOS=4 days)  and 11-days PO resulted in overall costs per patient of 2,540 USD, while branded and generic vancomycin exhibited 3466 USD and 3663 USD, respectively. The incremental cost of vancomycin-treated patients was driven by hospital daily charges, responsible for over 60% of the overall vancomycin costs. One-way sensitivity analysis revealed cost-savings for linezolid up to LOS≥9 days, with overall costs per patient ranging from 2540-4548 USD even if IV therapy was maintained throughout the inpatient period (LOS=15 days). CONCLUSIONS: Linezolid exhibited a cost-saving profile over branded or generic vancomycin for the treatment of SSTI-MRSA under the Brazilian public payer perspective. This economic benefit was a direct result of potential early discharge of patients receiving PO linezolid.