Context: Until recently, methicillin-resistant Staphylococcus aureus (MRSA) infections have been acquired primarily in nosocomial settings. Four recent deaths due to MRSA infection in previously healthy children in the Midwest suggest that serious MRSA infections can be acquired in the community in rural as well as urban locations. Objectives: To document the occurrence of community-acquired MRSA infections and evaluate risk factors for community-acquired MRSA infection compared with methicillin-susceptible S aureus (MSSA) infection. Design: Retrospective cohort study with medical record review. Setting: Indian Health Service facility in a rural midwestern American Indian community. Patients: Patients whose medical records indicated laboratory-confirmed S aureus infection diagnosed during 1997. Main Outcome Measures: Proportion of MRSA infections classified as community acquired based on standardized criteria; risk factors for community-acquired MRSA infection compared with those for community-acquired MSSA infection; and relatedness of MRSA strains, determined by pulsed-field gel electrophoresis (PFGE). Results: Of 112 S aureus isolates, 62 (55%) were MRSA and 50 (45%) were MSSA. Forty-six (74%) of the 62 MRSA infections were classified as community acquired. Risk factors for community-acquired MRSA infections were not significantly different from those for community-acquired MSSA. Pulsed-field gel electrophoresis subtyping indicated that 34 (89%) of 38 community-acquired MRSA isolates were clonally related and distinct from nosocomial MRSA isolates found in the region. Conclusions: Community-acquired MRSA may have replaced community-acquired MSSA as the dominant strain in this community. Antimicrobial susceptibility patterns and PFGE subtyping support the finding that MRSA is circulating beyond nosocomial settings in this and possibly other rural US communities.