OBJECTIVES: Skin and soft tissue infections caused by Staphylococcus aureus and Streptococcus pyogenes are a growing concern in Latin America due to the development of more complex resistance profiles to standard antibiotics. The aim of this analysis is to estimate the cost-effectiveness of Linezolid in the treatment of complicated skin and soft tissue infections (cSSTI) in Colombia. METHODS: A decision tree was built to estimate the incremental cost-effectiveness ratio of the Linezolid (600 IV/twice day) switch (600 orally/twice day) compared to Vancomycin (1 g IV/twice day), Daptomycin (4 mg IV/kg/day) and Tigecycline (100 mg IV followed by 50 mg twice day). The perspective was third payer including direct medical costs only. Effectiveness, safety and utility data were extracted from published literature. Unit costs were taken from health care institutions. Resource use and costs (drug acquisition, inpatient stay, healthcare professional visits, and lab tests) were considered for the model and expressed in 2012 US$. Time horizon was 28 days and effectiveness measures were quality-adjusted life-year (QALY’s) and percentage of patients cured. RESULTS: Total expected costs for each alternative were: Linezolid US$8,221.7, Vancomycin US$10,236.96; Daptomycin US$11,359.69 and Tigecycline US$11,255.92. Patients treated with Linezolid were associated with a shorter length of stay in the intensive care unit (7 days on average) which reduces overall treatment costs due it allows cSSTI patients switching from intravenous to oral administration (5 days reduction on average). Results for each alternative in terms of QALYs were: Linezolid 0.063, Vancomycin 0.060, Daptomycin 0.061 and Tigecycline 0.059. 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 would be a dominant treatment compared to Vancomycin, Daptomycin and Tigecycline. CONCLUSIONS: Linezolid seems to be a cost-saving option for the treatment of cSSTI in Colombia.