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Clostridium difficile infection (CDI) after total colectomy has been increasingly recognized over the past decade. C. difficile enteritis (CDE) is a rare occurrence, whereas C. difficile pouchitis (CDP) has been reported in approximately 10% of symptomatic patients seen at a referral center for pouch dysfunction. Similar to colonic CDI in the general population, antibiotic use and comorbid diseases may be risk factors for CDE. In contrast, the postoperative use of antibiotics does not seem to be associated with CDP, whereas male gender, recent hospitalization, and presurgery antibiotic use were shown to be risk factors for CDP. C. difficile is capable of colonizing all intestinal sites, including the ileal pouch. Similarities with the colon at physiological and cellular levels may contribute to the susceptibility of the ileal pouch to CDI. Postcolectomy CDI likely represents a disease spectrum from asymptomatic colonization to severe symptomatic infection. CDI should be considered in ostomy patients with fever and increased ileostomy output and in ileal pouch patients with a change in “normal” symptom pattern or chronic antibiotic-refractory pouchitis. Sensitive and specific methods for detection of CDI are available, and endoscopy is useful in evaluating the patient with suspected CDE or CDP, although pseudomembranes are typically absent. Vancomycin is used as the first-line therapy for CDP and may be warranted for patients with inflammatory bowel disease with CDE. Fecal microbiota transplantation has found its use in the management of severe or antibiotic refractory CDP, but this approach requires evaluation for the management of refractory CDE.