Obstructive sleep apnea is a well-known clinical manifestation of Prader-Willi syndrome. The aim of our study is to evaluate the efficacy of adenotonsillectomy for the treatment of the disorder as well as the improvement of their post-operative quality of life. Five patients with moderate to severe obstructive sleep apneas and adenotonsillar hypertrophy of grade III-IV underwent adenotonsillectomy. Pre- and postoperative apneas and Quality of Life were assessed respectively with a polysomnography with multi-sleep latency test and with the pediatric Quality of Life questionnaire, performed before and 6 months after surgery. A decrease of apnea/hypopnea index values has been detected between pre- and post-surgery (t=2.64, P=0.005), as well as oxygen desaturation index values (t=5.51, P=0.005), multi-sleep latency test (t=4.54, P=0.01), and of the values of pediatric Quality of Life questionnaire. No correlation has been detected between body mass index and apnea/hypopnea index, oxygen desaturation index and multi-sleep latency test values pre- and post-adenotonsillectomy. A correlation has been found between multi-sleep latency test and oxygen desaturation index values post-surgery (P=0.04). No post-operative complications were observed. Our data underline the efficacy of surgery in Prader-Willi patients with adenotonsillar hypertrophy in order to improve their quality of life.