OBJECTIVES: Skin and soft tissue infections (SSTI) is a common cause of morbidity, both in the community and within hospitals. Its treatment is limited to the increased likelihood of methicillin-resistant Staphylococcus Aureus (MRSA) which has been identified as the predominant cause of SSTI. In case of complicated SSTI (cSSTI) the probability of hospitalization raises generating higher healthcare costs. Therefore, the aim of this analysis was to estimate the budgetary impact of linezolid in the treatment of cSSTI from the Chilean public payer’s perspective. METHODS: A model was built within a three years timeframe to estimate the financial impact of different authorized therapies for cSSTI. Comparators were: linezolid (1200 mg/day), vancomycin (2 mg/day), daptomycin (350 mg/day) and tigecycline (100 mg/day). Only direct medical costs were considered. Resource use and costs (acquisition drug, inpatient stay, health care professional visits, and lab tests) were retrieved from Chilean health care institution databases (National Fund of Health – FONASA). Calculation of patients likely to be treatment was estimate using data published in the literature about the incidence of patients hospitalized SSTI and percentage of MRSA in cSSTI. Costs were expressed in 2012 US$ and univariate sensitivity analyses were performed. RESULTS: With an incidence of 0.164 hospitalizations for SSTI in the public sector per 10,000 hospital visits per year, and considering a market share growth of linezolid from 15% to 35% over three years, the model showed a reduction of approximately US$65,577.05 in overall costs for disease treatment (US$4 per patient); if the market share of linezolid would be increased 1% there could be savings for US$608,207.8 (first year). CONCLUSIONS: Linezolid is a favorable therapy for the treatment of cSSTI, considering the lower cost of treatment per patient (US$3489) compared with other available antimicrobial therapies, which would mean relevant savings to the National Fund of Health (FONASA) in Chile.