SummaryBackgroundThe association between autoimmune diseases and microscopic colitis remains uncertain.AimsTo describe the association between autoimmune diseases and microscopic colitis by using a matched case–control design based on nationwide registry data.MethodsAll adult Danish patients with a diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries. Odds of autoimmune diseases were compared between cases with microscopic colitis and sex‐ and age‐matched controls from the background population in a 1:10 ratio and evaluated by logistic regression calculating odds ratios (OR) with 95% confidence intervals (CI) adjusted for comorbidity. Analyses were stratified according to sex, age and the subtypes of lymphocytic and collagenous colitis.ResultsWe identified 15 597 cases with microscopic colitis and matched to 155 910 controls. In total, 3491 (22%) of patients with microscopic colitis had concomitant autoimmune disease compared to 16 521 (11%) of controls (OR, 2.46; 95% CI, 2.36‐2.56). Adjusting for comorbidities reduced the OR to 2.09 (95% CI, 2.01‐2.19). Analyses showed increased ORs with 16 different autoimmune diseases, particularly of gastrointestinal and endocrine origin, and connective tissue disorders. The highest ORs were for coeliac disease (OR = 10.15; 95% CI, 8.20‐12.6), Crohn’s disease (OR = 2.47; 95% CI, 2.10‐2.91) and ulcerative colitis (OR = 6.73; 95% CI, 6.20‐7.30). In stratified analyses younger age at diagnosis and collagenous colitis were associated with higher odds.ConclusionUsing nationwide registry data, microscopic colitis was associated with a wide range of autoimmune diseases, especially of gastrointestinal origin. The results suggest an autoimmune predisposition to microscopic colitis.