Background: Prader–Willi syndrome ( PWS) is a complex multisystem genetic disorder, is caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13. Multiple endocrine dysfunctions, including hypothyroidism, delayed or precious puberty, growth hormone deficiency, adrenal insufficiency, obesity, and diabetes mellitus, can be found in patients with PWS. The aim of this study was to investigate the prevalence of endocrine issues that needs medications in Korean patients with PWS. Methods: We performed a retrospective cohort study of the patients diagnosed clinically and genetically with PWS at Samsung Medical Center from 1994 to 2016. Their genetic aspects and medical records including blood chemistry, thyroid profile, and taking medications such as levothyroxine, gonadotropin analogues, oral hypoglycemic agents and insulins were analysis. Results: 274 patients (156 male, 118 female) were included at a median age of 11 years (1 month – 44 years). Hypothyroidism was found in 23 patients (8%), and the median age at diagnosis of hypothyroidism was 15 months (3 months – 22 years). Central precious puberty was found in 13 boys (8%) and 4 girls (3%) with PWS. Glucose intolerance was found in 53 (19%) patients. T2DM was found in 29 (10.6%) patients and their median age at diagnosis was 15 years. Of the 29 patients, seven had microvascular complication, with non-proliferative diabetic retinopathy in 6 of 7 cases. 51% had a deletion in chromosome 15q11-q13. There was no significant difference of endocrine issue according to genotype of PWS Conclusions: Our study gives an overview of endocrine dysfunctions that need medical treatments in patients with PWS. We suggest regular monitoring of endocrine issues including thyroid hormone, pubertal status, body mass index, and glucose homeostasis parameters to detect and treat endocrine problems early.