Until recently, methicillin-resistant Staphylococcus aureus (MRSA) has caused predominantly healthcare-associated infections. We studied MRSA infections and overall skin and soft tissue infections (SSTIs) in outpatients receiving care at the Baltimore Veterans Affairs Medical Center Emergency Care Service during 2001-2005. We found an increase in MRSA infections, from 0.2 to 5.9 per 1,000 visits (p < 0.01); most were community-associated SSTIs. Molecular typing showed that > 80% of MRSA infections were caused by USA300. In addition, SSTI visits increased from 20 to 61 per 1,000 visits (p < 0.01). The proportion of SSTI cultures that yielded MRSA increased from 4% to 42% (p < 0.01), while the proportion that yielded methicillin-sensitive S. aureus remained the same (10% to 13%, p = 0.5). The increase in community-associated MRSA infections and the overall increase in SSTIs in our population suggest that USA300 is becoming more virulent and has a greater propensity to cause SSTIs.