OBJECTIVES: To identify clinical risk factors for CDI and its recurrence among patients with IBD. DESIGN: Case-control cohort study of IBD patients with and without episodes of CDI. METHODS: A case-control study of 279 IBD patients with CDI. Medical history and IBD-related symptoms 3 months preceding a toxin-positive CDI were recorded and compared with age- and sex-matched IBD patients without CDI. Outcomes of CDI in IBD patients were recorded 2-6 months after CDI. RESULTS: Based on clinical symptoms and fecal calprotectin levels, IBD is active before CDI. Recently diagnosed IBD seemed to increase the risk for CDI. Corticosteroid usage frequently preceded CDI episodes. Advanced therapies were not associated with CDI. Antibiotic intake was not registered before CDI in 30% of the episodes. Recurrent CDI (rCDI) occurred in 30% (84/279) of IBD-CDI patients and 67% (90/135) of those episodes were registered within 90 days from the preceding episode. Most (79%) rCDI patients had ulcerative colitis (UC). CDI could complicate underlying IBD by increasing the need for escalation in IBD-related medical therapy and leading to hospitalization but it did not seem to increase the risk of colectomy. CONCLUSION: The major risk factors associated with CDI in IBD patients were IBD activity before infection, UC and colonic Crohn's disease, short duration of IBD, corticosteroid usage, and hospitalization. Patients with active IBD and a shorter disease duration may benefit from more frequent follow-ups in the early stages, as they appear to be at higher risk of developing CDI.