BackgroundGallstone disease is highly prevalent and is associated with systemic inflammation. AimsTo determine whether screen-detected gallstones or cholecystectomy are associated with the occurrence of autoimmune and autoinflammatory diseases and the most common subgroups thereof. MethodsA cohort study of three randomly selected general population samples from Copenhagen was performed. Participants (n = 5928) were examined in the period 1982–1992, underwent abdominal ultrasound examination to detect gallstone disease, and followed through national registers until December 2014 (median 24.7 years) for occurrence of immunological diseases. Multivariable Cox regression analyses were performed. ResultsGallstone disease was identified in 10% (591/5928) of participants, of whom 6.8% had gallstones and 3.2% had cholecystectomy at baseline. Gallstone disease was associated with incidence of autoimmune diseases (12.9% versus 7.92%; hazard ratio 1.46; 95% confidence interval [CI], [1.11;1.91]), diabetes mellitus type 1 (5.95% versus 3.67%; 1.53; [1.02;2.30]), and autoimmune thyroid disease (3.70% versus 1.59%; 2.06; [1.26;3.38]). Rheumatoid arthritis, autoinflammatory diseases, or any subgroups thereof were not associated. ConclusionsIn a large general population sample, screen-detected gallstone disease was associated with the development of autoimmune diseases during long-term follow-up. Future research efforts are needed to further explore common disease mechanisms.