We performed antimicrobial drug susceptibility testing and molecular typing on invasive methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 1,666) submitted to the University of Iowa Hygienic Laboratory during 1999-2006 as part of a statewide surveillance system. All USA300 and USA400 isolates were resistant to <or=3 non-beta-lactam antimicrobial drug classes. The proportion of MRSA isolates from invasive infections that were either USA300 or USA400 increased significantly from 1999-2005 through 2006 (p<0.0001). During 2006, the incidence of invasive community-associated (CA)-MRSA infections was highest in the summer (p = 0.0004). Age <69 years was associated with an increased risk for invasive CA-MRSA infection (odds ratio [OR] 5.1, 95% confidence interval [CI] 2.06-12.64), and hospital exposure was associated with decreased risk (OR 0.07, 95% CI 0.01-0.51).