OBJECTIVES: This study assessed length of stay (LOS), inpatient costs and mortality among hospitalized patients with cSSSI treated with ceftaroline compared with commonly used antibiotics to manage cSSSI (vancomycin, linezolid, daptomycin, tigecycline). METHODS: This retrospective study was conducted using the Premier's Perspective Comparative Database (2010-2013), which includes over 170 million inpatient records from ~500 hospitals in the US. Hospitalization records for adults (≥ 18 years) with a diagnosis of cSSSI (identified using ICD-9-CM codes) were selected. cSSSI-related hospitalization records with evidence of intravenous ceftaroline, vancomycin, daptomycin, linezolid or tigecycline were included. Using four separate logistic regression models propensity scores were estimated and patients in ceftaroline group were matched with patients in vancomycin, daptomycin, linezolid and tigecycline groups separately. Outcomes including LOS, inpatient costs and in-hospital mortality were compared among patients in ceftaroline group with the 4 other antibiotic groups using unadjusted (t-test and chi-square tests) tests.  RESULTS: The sample sizes in the matched cohorts were as follows: a) ceftaroline/ vancomycin n=2,834 (each group); b) ceftaroline/daptomycin n=2,651; c) ceftaroline/tigecycline n=2,606; d) ceftaroline/linezolid n=2,554. Mean duration for the study antibiotics ranged from 3.9 (vancomycin) to 4.6 (tigecycline) days. Average LOS and inpatients costs were significantly (all P-values <0.001) lower among patents in the ceftaroline group compared with patients in the vancomycin (mean LOS: 5.1 vs. 5.6;costs: $8,051 vs. $10,089), linezolid (LOS: 5.1 vs. 6.4;costs: $8,081 vs. $12,020), daptomycin (LOS: 5.0 vs. 6.3;costs: $7,824 vs. $10,227), tigecycline (LOS: 5.2 vs. 6.1;costs: $8,264 vs. $11,353) groups. In-hospital mortality rate was ~1% for ceftaroline, vancomycin, tigecycline and daptomycin groups (except linezolid group 2%). CONCLUSIONS: Previously two-large global clinical trials (CANVAS 1 and 2) confirmed clinical efficacy of ceftaroline in-comparison with vancomycin (standard-of-care) among patients with cSSSI. The current study serves as an initial-step towards confirming real-world effectiveness of ceftaroline in comparison with other commonly used antibiotics for cSSSI.