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To determine the prevalence of and explore possible differences in the risk for and symptoms ofClostridium difficileinfection between patients with and without inflammatory bowel disease (IBD).Stool specimens from subjects with and without IBD were evaluated for the presence ofC difficiletoxins. Demographic information, diagnosis, anatomic location, disease activity, IBD therapy, hospitalizations, and antibiotic and proton pump inhibitor (PPI) exposures were recorded.A total of 193 specimens were collected from 81 patients with IBD and 112 patients without IBD. The prevalence ofC difficileinfection was significantly greater in the patients with IBD than in those without IBD (P= .004; χ2 = 0.003; odds ratio = 3.3; 95% confidence interval = 1.5 to 7.6). In the patients with IBD, the prevalence of active disease was significantly greater in theC difficile—infected patients than in the uninfected patients (P< .0001). Colonic involvement was found in all patients with IBD. The specific type of IBD, IBD therapy, and antibiotic and PPI exposures that predisposed patients with IBD toC difficileinfection were not identified, whereas hospitalization was significantly more frequent in the patients without IBD (P= .025).Our findings indicate that in children, IBD is associated with an increased prevalence ofC difficileinfection. The specific risk factors reported in adults were not identified in these children, suggesting the possible involvement of other mechanisms for acquiring the pathogen.