Abstract Objective The risk of autoimmune disease could be increased in transgender (TG) persons and could be affected by TG care. We assessed the risk of autoimmune diseases in TG compared with controls before and after TG care. Methods A national register-based Danish cohort study in individuals diagnosed with gender dysphoria year 2000-2021. For each case, five age-matched cisgender controls of same birth sex and five age-matched controls of the opposite birth sex were included. Any autoimmune disease, type 1 diabetes and/or thyroid disease were study outcomes (International Classification of Diseases (ICD)-10 diagnosis and/or medical treatment for type 1 diabetes or thyroid disease). Results The cohort included 3812 TG and 38 120 controls. Before TG diagnosis, the incidence rate (IR) of type 1 diabetes was significantly higher in transmasculine persons (TM, n = 1993) compared with controls of same birth sex: incidence rate ratio (IRR) = 1.98 (1.16; 3.36). In transfeminine persons (TF, n = 1819) versus controls of same birth sex, the IRR for type 1 diabetes was 1.66 (1.05; 2.61) and for any autoimmune disease 1.35 (1.04; 1.77). Higher incidence of any autoimmune disease in TG was associated with higher age, medical morbidity, and psychiatric disease. After TG diagnosis, the IRR for thyroid disease was 1.98 (1.09; 3.61) in TF versus controls of same birth sex, whereas the IRR for remaining autoimmune outcomes were comparable between TG and controls of same birth sex. TM using GAHT had higher incidence of autoimmune disease 2.50 (1.10; 5.67) compared with nonusers. Conclusion Higher incidence of type 1 diabetes in TG compared with cisgender controls could be attenuated by TG care.