Despite the increasing burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, the risk factors are not well understood. We conducted a hypothesis-generating study using three parallel case-control studies to identify risk factors for CA-MRSA and community-associated methicillin-susceptible S. aureus (CA-MSSA) infections. In the multivariate model, antimicrobial use in the 1-6 months prior to culture was associated with CA-MRSA infection compared to CA-MSSA [adjusted odds ratio (aOR) 1·7, P=0·07] cases. Antimicrobial use 1-6 months prior to culture (aOR 1·8, P=0·04), history of boils (aOR 1·6, P=0·03), and having a household member who was a smoker (aOR 1·3, P=0·05) were associated with CA-MRSA compared to uninfected community controls. The finding of an increased risk of CA-MRSA infection associated with prior antimicrobial use highlights the importance of careful antimicrobial stewardship.