We assessed the role of Panton-Valentine leukocidin (PVL) and SCCmec type in community associated (CA) and healthcare associated (HC) Staphylococcus aureus (SA) skin/soft-tissue infections (STI). We prospectively monitored microbiology results (11 January 2005 to 6 January 2006), screened inpatients with SA in tissue samples or blood, and selected adults with STI. We recorded clinical/microbiological characteristics, and tested saved isolates for PVL genes (real time PCR) and SCCmec type (conventional multiplex PCR). We encountered 204 patients. MRSA strains that accounted for 70.5% CA and 66.0% HC cases, caused more abscesses (55.7% vs 29.7%; p =0.001) and were often PVL-positive (68.9% vs 4.8%; p <0.001). PVL-positive isolates caused more abscesses (72.9% vs 26.5%; p <0.001) but similar bacteremia (7.3% vs 7.1%). SCCmec IVa made up 95.8% of PVL-positive strains and accounted for 69.8% of the abscesses. SCCmec II caused higher mortality (14.8% vs 0-3.1%; p = 0.02). PVL was a predictor of abscesses (p <0.001). Predictors of bacteremia were age > or = 65 y (p =0.004), necrotizing infection (p =0.014), and head/neck location (p =0.05). These findings suggest that SCCmec type and PVL status influence STI manifestations and contribute to MRSA-MSSA differences. PVL is implicated in abscess formation but not bacteremia. Bacteremia is likely related to host condition and/or other virulence factors that were not studied.