Purpose <p>This study aimed to determine the detection rate of autoimmune polyendocrine syndrome (APS) among children with Graves’ disease (GD) at a single center and to compare clinical characteristics between those with isolated GD and those GD with APS (APS-GD).</p> Methods <p>A retrospective analysis was conducted on the clinical data of 555 patients and were categorized into isolated GD and APS-GD groups based on their progression status. The time for FT₄ to return to normal was used as an indicator of short-term treatment effectiveness.</p> Results <p>In all, 63 (11.4%) had coexisting APS; 52 (82.5%) were female. The most common component of APS was type 1 diabetes mellitus (T1DM) [24 (4.3%)]. Among APS-GD patients, after the diagnosis of the first component, the cumulative incidences of a second disease within the first, second, and third years were 63.4%, 74.6%, and 82.0%, respectively and till the end of the first decade reached 95.0%. The isolated GD group had higher levels of FT₃, TT₃, and TRAb. Under the same initial dosage, the median time for FT₄ to normalize was 22.0 (14.0, 30.0) d for the isolated GD group and 25.0 (13.5, 31.0) d for the APS group (<i>P</i> = 0.936).</p> Conclusion <p>The study uncovered a high comorbidity rate of APS in children with GD, suggesting that patients with APS-GD have a higher risk of progression to additional endocrine gland disorders. Yet, both groups showed no significant difference in their short-term therapeutic response. These findings are crucial for guiding the clinical management and follow-up of pediatric GD patients.</p>