OBJECTIVES: To analyze the cost-minimization of Daptomycin in comparison to Vancomycin and Linezolid for patients with Methicillin Resistant Staphylococcus Aureus (MRSA) skin and soft tissues infections in Brazilian private payer perspective. METHODS: The alternatives were indirectly compared due to the absence of Head to Head studies. Resource consumption for MRSA treatment were collected from previous publication and divided into two categories: hospital care (including diagnostic tests) and pharmaceuticals. Total treatment cost was investigated for a base case where patients were treated in the best profile for each medicine effectiveness based on values extracted from randomized open or blind studies [Daptomycin: Length of stay (LOS) = 4 days with intravenous drug. Vancomycin: LOS = 7 days with intravenous drug. Linezolid: LOS = 4 days with intravenous drug and 11 days with oral drug]. The costs data regarding medicines were collected from companies price list or price submission process and utilization costs from literature. Results were converted in US Dollars (R$ 1.7/USD 1.00). A one-way sensitivity analysis was performed. RESULTS: For base case the total treatment was US$1,646.89 for Daptomycin,  US$1,843.84 for Vancomycin and US$3,290.46 for Linezolid. Pharmaceutical inpatient cost was US$ 129.93 higher for Daptomycin in comparison with Linezolid and US$868,31 higher when compared with generic-vancomycin; however this cost was offset by shorter LOS. Despite the unitary prices of the Vancomycin and Linezolid are lower than the price of Daptomycin, the total treatment costs with Linezolid and generic-vancomycin is higher than with Daptomycin. The sensitivity analysis on costs variables in an interval of +/-20%, was robust with the base case. CONCLUSIONS: The Daptomycin is a cost-saving alternative for MRSA skin and soft tissues infections compared to generic-vancomycin and linezolid in the perspective of Brazilian private payer.