Prader-Willi syndrome (PWS) is a complex genetic disorder and represents the most common genetic cause of life-threatening obesity in childhood and adolescence. The indication for bariatric surgery in children and adolescents with syndromic obesity is still controversial. This case report deals with the preoperative medical and psychosocial evaluation of a 16-y-old male adolescent with PWS who underwent sleeve gastrectomy. Information on a 6-mo follow-up is also reported. The preoperative body weight was 223 kg (body mass index [BMI] 80.9 kg/m2). Comorbidities included severe obstructive sleep apnea with nocturnal respiratory failure, hypertension, and impaired glucose tolerance. At 2- and 6-mo follow-ups, the percent excess weight loss was 16 (BMI 71.8 kg/m2) and 29.2 (BMI 64.6 kg/m2), respectively. Comorbities did improve. Intellectual disability of genetic origin per se may not represent an absolute contraindication to bariatric surgery if adequate and tailored clinical and psychosocial support is provided.