OBJECTIVES: CA-MRSA has become increasingly common; however, clinical characteristics and outcomes differentiating CA-MRSA from CA-MSSA are unclear. We compared long-term outcomes of adults with CA-MRSA to those with CA-MSSA. METHODS: This was a prospective, observational study in 13 primary care clinics within the South Texas Ambulatory Research Network (STARNet). Classification of MRSA and MSSA, and antibiotic susceptibility were determined using the Vitek System (bioMérieux). Treatment failure was defined as one of the following within 90 days of the initial visit: (1) change in antibiotic therapy, (2) incision and drainage (I&D), (3) SSTI at a new site, (4) SSTI at the same site, (5) emergency department visit, or (6) hospitalization. Patients were considered to have “moderate or complicated” SSTIs if they had a lesion ≥ 5 cm in diameter or diabetes mellitus. Comparisons between groups were performed using the χ2 test and Student's t test, as appropriate. RESULTS: Among 104 patients with community-associated Staphylococcus aureus SSTIs, the overall treatment failure rate at 90 days was 20%. The occurrence of treatment failure was similar among patients with CA-MRSA infections and those with CA-MSSA infections (13 of 68 [19%] vs. 8 of 36 [22%] patients; P=0.71). No significant differences were found in patient demographics, clinical characteristics including infection severity and treatment approach, or type of treatment failure. Patients with moderate or complicated SSTIs (P=0.03), and those who described signs and symptoms of infection for > 7 days prior to initial clinic visit (P=0.02), were associated with treatment failure. CONCLUSIONS: Although it is believed that patients with CA-MRSA SSTIs may have more serious outcomes than CA-MSSA SSTIs, we found similar outcomes in these two groups in the primary care setting. Treatment failures were associated with infection severity and duration of infection for seven days or longer prior to seeking care.