OBJECTIVES: Current guidelines for the treatment of acute bacterial skin and skin structure infections (ABSSSI) recommend aggressive treatment, including hospitalization for patients whose infection is progressing despite empiric antibiotic therapy. In such cases potentially involving S. aureus, guidelines suggest that clinicians should use agents effective against MRSA because of the high prevalence of community-associated MRSA strains. This study attempts to ascertain the US economic burden and near-term outcomes of in-hospital treatment of ABSSSI during recent years. METHODS: Using the Premier Hospital Database, hospitalization records were reviewed from 2007 to 2009 to extract patients with principle diagnosis of ICD-9 codes for cellulitis, abscess, postoperative and traumatic wound infections, and other conditions related to ABSSSI. We assessed inpatient utilization in terms of LOS and ICU time, and inpatient costs stratified by initial antibiotic treatment.  We also assessed the frequency of in-hospital mortality and empiric treatment failure. RESULTS: Inpatient treatment of ABSSSI increased by 15.4% from 2007 to 2009. In 2009, 110,457 ABSSSI patients were admitted to Premier hospitals, with 65% admitted through the ER.  The initial antibiotic treatment was vancomycin (49.9%) and clindamycin (15.9%). The average LOS was 5.3 days. The average cost per stay was $8000. The most costly departmental charges were room/board ($1000) and pharmacy ($650). 17.2% of patients failed on initial antibiotic treatment, resulting in additional LOS of 5 days and $6000 per stay on average. With approx. 750K admissions for ABSSSI in the United States, this extrapolates to a US hospital economic burden of >$6 billion/yr. CONCLUSIONS: The economic burden of hospitalization for ABSSSI in the United States is significant. Antibiotic treatments offering the possibility of treating a greater proportion of patients currently hospitalized in an ambulatory or observational setting by avoiding or shortening hospital stays may significantly reduce the cost to the US health care system.