Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are common in southwestern Alaska. Outbreak strains have been shown to carry the genes for Panton-Valentine leukocidin (PVL). To determine if carriage of PVL-positive CA-MRSA increased the risk for subsequent soft tissue infection, we conducted a retrospective cohort study by reviewing the medical records of 316 persons for 3.6 years after their participation in a MRSA nasal colonization survey. Demographic, nasal carriage, and antimicrobial drug use data were analyzed for association with skin infection risk. Skin infections were more likely to develop in MRSA carriers than in methicillin-susceptible S. aureus carriers or noncarriers of S. aureus during the first follow-up year, but not in subsequent years. Repeated skin infections were more common among MRSA carriers. In an area where PVL-containing MRSA is prevalent, skin infection risk was increased among MRSA nasal carriers compared with methicillin-susceptible S. aureus carriers and noncarriers, but risk differential diminished over time.