Background: Adults with inflammatory bowel disease (IBD) have a high prevalence of Clostridium difficile carriage, but little data exist regarding pediatric patients with IBD. Serum antibody responses to C. difficile toxins in correlation with organism carriage are not described in IBD. This study determines the prevalence of C. difficile carriage and compares serum antibody responses to C. difficile toxins in pediatric outpatients with IBD and controls. Methods: Fecal and serum samples were prospectively collected from pediatric outpatients with IBD (n = 85) and age-matched controls (n = 78). Initial and follow-up stool samples were tested using cytotoxigenic C. difficile culture and PCR to detect the toxin B gene. Pulsed-field gel electrophoresis determined the strain type. Enzyme-linked immunosorbent assay determined serum immunoglobulin responses to C. difficile toxins. Results: Asymptomatic C. difficile carriage was significantly greater in IBD (17%) versus controls (3%) (P = 0.012). IBD type, disease severity, IBD therapy, recent antibiotics, and hospitalizations were not associated with carriage. Proton pump inhibitor use was significantly higher in patients with C. difficile carriage (54% versus 25%, P < 0.05). North American pulsed-field (NAP) strain carriage varied over time in patients colonized with C. difficile. A significantly greater proportion of patients with IBD had a positive serum antibody response to toxin A (69%) compared with controls (53%) (P < 0.05). Conclusions: Asymptomatic toxigenic C. difficile carriage was increased in pediatric outpatients with IBD compared with controls. Proton pump inhibitor use was associated with increased carriage. Antibody responses to C. difficile toxins were increased in IBD, potentially promoting asymptomatic colonization. Future studies should identify the risk factors for symptomatic C. difficile in pediatric IBD. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.