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Interestingly, Clostridium difficile infection (CDI) worsens the course of inflammatory bowel disease (IBD); however, there is a paucity of data regarding the treatment of CDI in this group of patients.This was a prospective, single-blind trial. Children with flare of IBD and CDI were randomly assigned to receive metronidazole or rifaximin orally for 14 days. CDI was diagnosed based on a positive well-type enzyme immunoassay (EIA) toxins A/B stool test for C. difficile toxins A and/or B. The cure rate was defined as the percentage of patients with a negative EIA stool test for C. difficile toxins A/B measured 4 weeks after the end of treatment. Recurrence was defined as a repeat CDI within 2 to 8 weeks.In total, we included 31 patients with IBD including 12 patients with Crohn's disease and 19 with ulcerative colitis. Of them, 17 received metronidazole and 14 received rifaximin. There were no statistically significant differences between the 2 study groups including age, type of treatment, and disease activity. There was no statistically significant difference in the cure rate between patients treated with metronidazole and rifaximin (70.6% versus 78.6%, respectively, P = 0.5). We found no difference in recurrence rate between the 2 study treatment types (17% versus 0%, respectively, P = 0.3). We did not find an association between immunosuppressive therapy and CDI cure rate or CDI recurrence rate.Metronidazole and rifaximin were similarly effective treatments for CDI in pediatric patients with IBD.