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Recent studies suggest that inflammatory bowel disease (IBD) may share an underlying pathogenesis with other autoimmune diseases.Two United States data sets with patient-level medical and drug claims were used to explore the occurrence of autoimmune diseases in patients with IBD, particularly Crohn's disease (CD) and ulcerative colitis (UC), with that in controls. From 2001 to 2002 IBD patients were identified using International Classification of Diseases, 9th revision, diagnosis codes in the IMS Health Integrated Administration Claims Database and the Market Scan Commercial Claims and Encounters Database. Controls were selected by matching on sex, age, Census Bureau region, and length of previous medical insurance coverage. Odds ratios (ORs) evaluated the risk relationship between IBD patients and controls within an estimated Mantel-Haenszel 95% confidence interval. Sensitivity analysis tested the case identification method used to select IBD patients.The risk for ankylosing spondylitis (AS) was substantially increased across both data sets: OR (95% confidence interval [CI]) of 7.8 (5.6–10.8) in IMS Health and 5.8 (3.9–8.6) in MarketScan. The risk for rheumatoid arthritis (RA) was 2.7 (2.4–3.0) and 2.1 (1.8–2.3), respectively; for multiple sclerosis (MS); the ORs were 1.5 (1.2–1.9) and 1.6 (1.2–2.1), respectively. There was no increased risk for type 1 diabetes mellitus, and the results for psoriatic arthritis (PsA) were inconsistent. The sensitivity analysis supported these findings.A much higher risk for RA, AS, PsA, and MS was observed in IBD patients compared with controls. Prospective epidemiologic studies are needed to confirm these findings and explore the pathogenic mechanism of this relationship.