Background and Aims. Prader-Willi syndrome (PWS), the most common genetic cause of obesity, is characterized by elevated morbility and mortality in all ages. In this context, non-obese PWS children showed low frequency of metabolic syndrome (MetS), while that observed in obese PWS children was very close to those of obese controls. Aim of the study was to estimate the occurrence of MetS and its components in a large group of PWS adults, according to obesity status. Methods and Results. A cross-sectional study was performed in 108 PWS aged 18.0-43.2 years (87 obese and 21 non-obese) and in 85 simple obese controls matched for age, gender, and also for BMI with obese PWS. Non-obese PWS showed lower waist circumference, insulin, HOMA index, triglycerides, diastolic blood pressure, and higher HDL-C than both obese PWS and controls (p