OBJECTIVES: Complicated skin and skin structure infections (cSSSIs) are primarily caused by gram-positive bacteria, including Staphylococcus aureus and β-hemolytic streptococci. The impact of cSSSIs caused by Methicillin-resistant S. aureus (MRSA) has been associated with an increase in length of hospital stay and resource use. The aim of this analysis is to estimate the cost-effectiveness of linezolid in the treatment of cSSTI at the Chilean public setting. METHODS: A decision tree was built to estimate the incremental cost-effectiveness ratio of linezolid (1200 mg/day) compared to vancomycin (2 mg/day), daptomycin (350 mg/day) and tigecycline (100 mg/day). The payer’s perspective (National Fund of Health – FONASA) was used, including inpatient medical costs only. The time horizon was 28 days. Effectiveness was measured with quality-adjusted life-year (QALY’s) and the percentage of patients cured. Efficacy, safety and utility values were retrieved from literature. Resource use and costs (drug acquisition, inpatient stay, healthcare professional visits, and lab tests) were taken from Chilean public healthcare institutions. Costs are expressed in 2012 USD. RESULTS: The total expected costs per patient were: linezolid US$3489.0, vancomycin US$3909.2, daptomycin US$6131.2 and tigecycline US$5509.0. The treatment with linezolid was associated with a shorter stay in the intensive care unit (7 days on average) which reduces the cost of treatment because it allowed the switch from intravenous to oral administration (5 days on average). Results for each alternative in QALYs were: linezolid 0.063, vancomycin 0.060, daptomycin 0.061 and tigecycline 0.059. The results for each alternative in terms of percentage of patients cured were: linezolid 84.4%, vancomycin 74.7%, daptomycin 78.1% and tigecycline 70.4%. The model results indicate that linezolid is dominant compared to vancomycin, daptomycin and tigecycline. Probabilistic sensitivity analyses showed the robustness of these findings. CONCLUSIONS: Linezolid is a cost-saving alternative in the treatment of cSSTI in the Chilean National Fund of Health (FONASA).