BACKGROUND: The purpose of our work was to provide a data-driven perspective to autoimmune polyglandular syndrome (APS), a complex autoimmune disorder, supplementing traditional clinical observations. METHODS: Medical records of 7559 patients were analyzed, and autoimmune origin was proved in 3180 cases of which 380 (12%) had APS. Associations of component disorders were investigated by computational methods to reveal typical patterns of disease development. RESULTS: Twenty-eight distinct autoimmune disorders were diagnosed forming 113 combinations. The 10 most frequent combinations were responsible for 51.3% of cases. Hashimoto's thyroiditis (HT) and Graves' disease (GD) were differentiated as the main cornerstones of APS, sharing several comorbidities. HT was the most common manifestation (67.4%), followed by GD (26.8%) and type 1 diabetes mellitus (T1D) (20.8%). APS started significantly earlier in men than in women. Thyroid autoimmunity was frequently linked to gastrointestinal and systemic manifestations, and these patterns of associations substantially differed from that of T1D, Addison's disease, or coeliac disease when present as first manifestations, suggesting the possibility of a common biological cause. CONCLUSION: APS is more frequent than reported. Classifying APS requires a shift of perspective toward disease associations rather than disorder prevalence.