We compared characteristics of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) and CA-MRSA invasive disease identified in Minnesota from 2000 through 2003. A total of 586 patients with SSTIs and 65 patients with invasive disease were identified. Patients with invasive disease were more likely to be smokers (p = 0.03), and report a history of immunosuppressive therapy (p = 0.03), emphysema (p = 0.011), or injection drug use (p = 0.020) than were SSTI patients. Invasive disease isolates were less likely to be susceptible to ciprofloxacin (p = 0.002) and clindamycin (p = 0.001) and more likely to have healthcare-associated pulsed-field gel electrophoresis subtypes than SSTI isolates (p<0.001). Patients with invasive disease may have had healthcare exposures that put them at risk of acquiring healthcare-associated MRSA and which were not exclusion criteria in the CA-MRSA case definition. Continued surveillance of MRSA is needed to better characterize CA-MRSA infections.