OBJECTIVES: Rising health care costs and financial penalties have necessitated treatment strategies for ABSSSI that avoid hospital admissions and reduce length of stay(LOS), hospital acquired infections(HAIs), and readmissions. Providing parenteral antibiotic therapy in OP settings provides an opportunity to shift care outside the hospital to free hospital beds and reduce additional LOS from HAIs. This analysis estimated, from a US payer perspective, cost offsets of treating gram+ ABSSSIs with varied hospital LOS followed by OP care. METHODS: Economic drivers of care were estimated using a literature-based economic model incorporating inpatient(IP) and OP components. The model incorporated equal efficacy, adverse events(AE), resource use, and costs from literature and public sources. Once and twice daily OP infusions to achieve a 14-day treatment were tested to determine cost offsets shifting IP days to OP days. Sensitivity analyses were performed. Costs were adjusted to 2012US$. RESULTS: Total non-drug medical cost for ABSSSI ranged from $8,790-$15,968 for 3 and 7 days IP, respectively, while treatment entirely OP to avoid admission ranged from $3692-$4353. IP medical costs included IP bed-day($1853) and AE costs($343). OP care included either daily home care($194) or infusion center fee($154), PICC line with fluoroscopy($786), PICC complications($188), labs($102), and physician visit($222) for evaluation of ABSSSI.  IP versus OP cost breakdown was: 3 days IP($5,902)/11 days OP($2,888-$3,429); 7 days IP($13,314)/7 days OP($2,273-$2,654). Sensitivity analyses revealed OP cost drivers to be IV days, infusion/OP care costs, and PICC costs versus LOS, bed-day cost, and IV days for IP drivers.   CONCLUSIONS: Shifting ABSSSI care to OP settings may result in cost savings up to 44%, with potential to prevent HAIs. Typical OP scenarios represent ~33% of total medical cost, with PICC accounting for 28-43% of OP burden. Value of new ABSSSI therapies will be driven by eliminating need for PICC line and ability to reduce/avoid hospital days.