OBJECTIVES: Meticillin-resistant staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant healthcare-associated infections worldwide. Its prevalence remains high in the Greek hospital setting. Complicated skin and soft tissue infections (cSSTIs) due to MRSA are associated with prolonged hospitalization, additional costs of care and significant morbidity. The purpose of this study was to conduct a budget impact analysis relative to different management scenarios for MRSA-cSSTIs from a hospital perspective. METHODS: Equal efficacy for the pharmacotherapies under evaluation was assumed and resource use was elicited via an expert panel. The model was based on a decision tree for the management of hospitalized patients with MRSA-cSSTIs, simulating costs and outcomes for the duration of hospitalization according to the therapeutic scenario, including empiric and first-line therapies. Inpatient costs consisted of hospitalization, diagnostic, medical and antibiotic costs. Economic results (Euros 2013) reflect the hospital setting. RESULTS: Total per patient cost according to first-line agent was €2,458, €2,730, €2,850, €3,495 and €3,098 and mean length of stay (LOS) was 9.2, 12.5, 10.3, 13.0 and 14.0 days for linezolid, vancomycin, daptomycin, tigecycline, teicoplanin respectively. An estimated 10,287 MRSA-cSSTI patients are treated annually in Greek hospitals. Thus, by increasing the use of linezolid by 11% over a three-year period, for the management of MRSA-cSSTIs, this could result in savings of €873,141 for the hospital budget (current:€29,081,597, projected:€28,749,994 with savings of €190,016-year 1, €351,523-year 2 and €331,602-year 3). By reducing the LOS for linezolid patients from 9.2 days (current LOS in Greece as per expert panel) to 7.6 days to match data from a large phase IV study in MRSA-cSSTIs (Itani 2010), potential savings amount to €1,870,700 for the three year period. CONCLUSIONS: The analysis corroborates literature findings with regards to the early switch/early discharge potential and outcomes due to oral antibacterial switching in cSSTIs. Increased use of linezolid in the treatment of MRSA-cSSTIs could result in substantial savings for the Greek hospital budget.