Prader-Willi syndrome (PWS) is one of the 25 syndromic forms of obesity, in which patients present—in addition to different degrees of obesity—intellectual disability, endocrine disturbs, hyperphagia and/or other signs of hypothalamic dysfunction. In front of a severe/extreme obesity and the failure of non-invasive treatments, bariatric surgery is proposed as a therapeutic option. The complexity of the clinical condition, which could affect the long-term effects of bariatric surgery, and the frequent association with a mild to severe intellectual disability raise some ethical concerns in the treatment of obese PWS adolescents. This article analyses these issues referring to the principles of healthcare ethics: beneficence/non-maleficence (proportionality of treatments; minimisation of risks); respect of autonomy; justice. Based on these principles, three hypothetical scenarios are defined: (1) obese PWS adolescent, capable of making an autonomous decision; (2) obese PWS adolescent with a severe intellectual disability, whose parents agree with bariatric surgery; (3) obese PWS adolescent with a life-threatening condition and a severe intellectual disability, whose parents do not agree with bariatric surgery. The currently available evidence on efficacy and safety of bariatric surgery in PWS adolescents with extreme or severe obesity and the lack of adequate long-term follow-up suggests great caution even in a very life-threatening condition. Clinicians must always obtain a full IQ assessment of patients by psychologists. A multidisciplinary team is needed to analyse the clinical, psychological, social and ethical aspects and organise support for patient and parents, involving also the hospital ethical committee or, if necessary, legal authorities.