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We determined estimated incidence of and risk factors for community-associated Clostridium difficile infection (CA-CDI) among patients treated at 6 North Carolina hospitals. CA-CDI case-patients were defined as adults (>18 years of age) with a positive stool test result for C. difficile toxin and no hospitalization within the prior 8 weeks. CA-CDI incidence was 21 and 46 per 100,000 person-years in Veterans Affairs (VA) outpatients and Durham County populations, respectively. VA case-patients were more likely than controls to have received antimicrobial drugs (adjusted odds ratio [aOR] 17.8, 95% confidence interval [CI] 6.6–48] and to have had a recent outpatient visit (aOR 5.1, 95% CI 1.5–17.9). County case-patients were more likely than controls to have received antimicrobial drugs (aOR 9.1, 95% CI 2.9–28.9), to have gastroesophageal reflux disease (aOR 11.2, 95% CI 1.9–64.2), and to have cardiac failure (aOR 3.8, 95% CI 1.1–13.7). Risk factors for CA-CDI overlap with those for healthcare-associated infection.