Worldwide, Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is the most frequently identified pathogen causing complicated skin and skin structure infections (cSSSI). MRSA isolates are classified by staphylococcal cassette chromosome mec (SCCmec) type, with health care-associated MRSA (HA-MRSA) associated with types I, II, III and community-associated MRSA (CA-MRSA) with type IV (often carrying Panton-Valentine leukocidin, PVL). This study sought to determine the impact of MRSA SCCmec type on outcomes of cSSSI patients treated with linezolid or vancomycin. A total of 465 MRSA isolates from patients treated with linezolid (600 mg every 12 h orally/intravenously) or vancomycin (15 mg/kg every 12 h intravenously with dose adjustment) from 2004 to 2007 were subjected to SCCmec typing, PVL screening, MIC determination, and clinical/microbiological outcome evaluation (6-28 days post last dose). The most common SCCmec type was Type IV (PVL positive, n=236, CA-MRSA). Clinical and microbiological outcomes for linezolid and vancomycin were analyzed by SCCmec type. Vancomycin clinical success rate for CA-MRSA and HA-MRSA isolates with vancomycin MIC of 2 μg/ml was both 50%. Five heterogeneously vancomycin-intermediate S. aureus (hVISA) isolates were identified (none CA-MRSA), with 3/3 linezolid-treated patients successful and 1/2 vancomycin-treated patients failing. Outcomes were independent of SCCmec type for both drugs, with no mortality differences by type. These findings suggest linezolid and vancomycin are clinically effective for cSSSI caused by all SCCmec types of MRSA, including HA-MRSA (types I, II, III) and CA-MRSA (type IV).