OBJECTIVES: Develop model simulating economic implications of alternative treatment strategies for acute bacterial skin and skin structure infections (ABSSSIs) with suspected Methicillin-Resistant Staphylococcus aureus (MRSA) that considers antibiotic switches, course duration, route of administration and location of care (LOC). METHODS: Discrete event simulation (DES) tracks patient pathways through various LOC (ED, inpatient, outpatient) during ABSSSI treatment for suspected MRSA. Model assumes 60% of patients hospitalized. Multiple pathways are allowed: patients responding can move to outpatient to finish treatment, switch treatment at discharge or receive 2nd line treatment if not responding. Patients accrue resource use, time in LOC and costs. Hospital days obtained from analysis of Premier Hospital Database. Three cohorts created; all assigned to receive vancomycin (VAN) 1stline therapy. Upon discharge, one cohort continued on VAN, one switched to oral linezolid (LIN), one to daptomycin (DAP) to complete treatment. Costs are from the Medicare perspective in 2012 USD. RESULTS: Hospital plus outpatient days range from 11.1 (VAN) to 14.5 (LIN); costs ranged from $6,983 (LIN) to $8,122 (VAN) with suspected MRSA. By comparison, reatment duration ranged from 9.97 (VAN) to 13.02 (LIN) and total costs ranged from $6,889 (LIN) to $9,354 (VAN) when MRSA is not always suspected. Despite longer LIN treatment, costs are lower because of avoided infusion costs. Outpatient costs account for 22% (LIN) to 33% (VAN) of total costs.  Sensitivity analysis examined impact on cost when treatment duration varied per drug labeling. Total costs varied from $6,756 to $7,158 when duration of LIN ranges from 8 days to 12 days. CONCLUSIONS: Treatment choice and LOC have major impact on ABSSSI resource use and costs. Suspected MRSA increases treatment duration and cost. Economic implications for payers and providers should be evaluated using models that capture these elements in view of long-acting lipoglycopeptide IV antibiotics in development that avoid repeated infusions and may allow for less inpatient treatment.