The purpose of this study was to determine the extent of the spread of epidemic clones of non-multiresistant methicillin-resistant Staphylococcus aureus (nmMRSA) and the epidemiology of resultant infections throughout the state of Queensland. We collected a sample of clinical isolates of nmMRSA from laboratories serving public hospitals and clinics throughout the state. Three hundred isolates were typed and tested for the presence of Panton-Valentine leukocidin (PVL) genes and demographic and clinical data were collected from associated cases. Fifteen percent of S. aureus isolates were nmMRSA and 69% of these belonged to PVL-positive clones, predominantly ST93 and CC30. Low numbers of USA300- and USA400-like isolates were also present. Infections due to PVL-positive strains were much less frequently acquired in hospital (3.4%) than those due to PVL-negative nmMRSA (23.7%). Thirty-seven percent of cases were in indigenous people who make up only 3.6% of the general population. The proportion of cases with PVL-positive, but non-negative isolates decreased progressively with age, suggesting that immunity to PVL might be an important determinant of protection. nmMRSA strains are present throughout Queensland and cause infections in both community and healthcare settings.