OBJECTIVES: To evaluate the potential economic implications of alternative treatment strategies for acute bacterial skin and skin structure infections (ABSSSIs) by capturing the impact of the initial empiric antibiotic selection, switches to 2nd line antibiotics, course length, route of administration and location of care. METHODS: The treatment pathway of each patient is simulated through various locations (emergency department (ED), inpatient, and outpatient). Patients responding at 72 hours may transfer to the outpatient setting to complete the course, switch antibiotic at discharge or receive 2nd line treatment due to lack of response or relapse. Analysis of US inpatient claims (Premier Hospital Database) provided length of stay information. Results from three scenarios are presented - each cohort was assigned to 1st line vancomycin (VAN). At discharge, one cohort completed the VAN course, one switched to oral linezolid (LIN) and the other to daptomycin (DAP). Costs (2012 USD from the Medicare perspective) and time in each location are accrued throughout the entire treatment course. RESULTS: Compared to VAN (10.1), hospital plus outpatient days were greater with LIN (13.4) and DAP (10.8), but total costs were reduced by $2,465 and $252 with LIN and DAP respectively, suggesting avoiding repeated outpatient infusion center visits lowers costs. Outpatient care comprises 32% (LIN) to 50% (VAN) of total costs and will remain important to consider as treatment pathways move further towards the outpatient setting. CONCLUSIONS: The choice of antibiotic and location of care have a substantial impact on resource use and costs. The economic implications of new treatment options currently in development such as long-acting lipoglycopeptide IV antibiotics (oritavancin and dalbavancin), which avoid repeated infusions and are anticipated to allow providers to shift more care to the ambulatory setting, can be assessed using the modeling framework presented here.