OBJECTIVES: Complicated skin and soft tissue infections (cSSTI) are commonly encountered in the community and nosocomial settings. Methicillin-resistant S. aureus(MRSA) has become the predominant pathogen in cSSTI raising health care costs and reducing positive health outcomes. The aim of this analysis is to estimate the cost-effectiveness of linezolid in the treatment of cSSTI in Chile from the private payer’s perspective. METHODS: A decision tree was built to estimate the incremental cost-effectiveness ratio (ICER) of linezolid (1200 mg/day) compared with vancomycin (2 mg/day), daptomycin (350 mg/day) and tigecycline (100 mg/day). Within a time horizon of 28 days, the model simulates health outcomes and costs for all alternatives at the Provisional Health Institutions – ISAPRE. Only direct medical costs were considered. Effectiveness measures were: quality-adjusted life-year gained (QALY’s) and percentage of patients cured. Efficacy, safety and utility values were collected from literature review. Resource use and medical costs (drug acquisition, inpatient stay, healthcare professional visits, and lab tests) were taken from Chilean private institutions. Costs are expressed in 2012 US$. RESULTS: The total expected costs for per patient were: linezolid US$12,905.1, vancomycin US$13,039.9, daptomycin US$16,067.3 and tigecycline US$17,038.5. Treatment with linezolid was associated with a shorter length of stay at the intensive care unit (7 days on average) which reduced significant treatment costs due the likelihood of switching from intravenous to oral administration (5 days savings on average). Results for each alternative in terms of QALYs were: linezolid 0.063, vancomycin 0.060, daptomycin 0.061 and tigecycline 0.059. The percentage of patients cured for each alternative was: linezolid 84.4%; vancomycin 74.7%; daptomycin 78.1% and tigecycline 70.4%. Model result suggests that linezolid would be dominant compared to vancomycin, daptomycin and tigecycline. CONCLUSIONS: Despite its higher acquisition cost, linezolid would be a cost-saving alternative in the treatment of cSSTI in the Chilean Provisional Health Institutions (ISAPRE).