Non-multiresistant methicillin-resistant Staphylococcus aureus (nmMRSA) infections are emerging worldwide and are often community-associated. This prospective case-cohort study compares features of 96 nmMRSA clinical isolates with 96 matched multiresistant MRSA (mMRSA) and 192 matched methicillin-susceptible S. aureus (MSSA) clinical isolates. Seventy-four percent of nmMRSA infections were healthcare-associated. nmMRSA infections were much more likely to involve skin and soft tissue (skin and soft tissue infections; SSTIs) and were much less likely to be treated appropriately with antibiotics than MSSA or mMRSA infections. Panton-Valentine leukocidin (PVL) genes were detected in 55% of nmMRSA, 16% of MSSA and 2% of mMRSA isolates. Independent of the methicillin-resistance phenotype, 59% of PVL-positive SSTIs presented as furunculosis compared to only 10% of PVL-negative SSTIs. Patients with PVL-positive infections were much younger than patients with PVL-negative infections. The proportion of PVL-positive infections peaked in the 10-29 years old age group, followed by a linear decline.