Background: Community-associated methicillinresistant Staphylococcus aureus (CA-MRSA) infections have emerged among patients without health careassociated risk factors. Understanding the epidemiology of CA-MRSA is critical for developing control measures.Methods: At a 464-bed public hospital in Chicago and its more than 100 associated clinics, surveillance of soft tissue, abscess fluid, joint fluid, and bone cultures for S aureus was performed. We estimated rates of infection and geographic and other risks for CA-MRSA through laboratory-based surveillance and a case-control study.Results: The incidence of CA-MRSA skin and soft tissue infections increased from 24.0 cases per 100 000 people in 2000 to 164.2 cases per 100 000 people in 2005 (relative risk, 6.84 [2005 vs 2000]). Risk factors were incarceration (odds ratio [OR], 1.92; 95% confidence in-terval [CI], 1.00-3.67), African American race/ethnicity (OR, 1.91; 95% CI, 1.28-2.87), and residence at a group of geographically proximate public housing complexes (OR, 2.50; 95% CI, 1.25-4.98); older age was inversely related (OR, 0.89; 95% CI, 0.82-0.96 [for each decade increase]). Of 73 strains tested, 79% were pulsed-field gel electrophoresis type USA300.Conclusions: Clonal CA-MRSA infection has emerged among Chicago's urban poor. It has occurred in addition to, not in place of, methicillin-susceptible S aureus infection. Epidemiological analysis suggests that control measures could focus initially on core groups that have contributed disproportionately to risk, although CA-MRSA becomes endemic as it disseminates within communities.