Various epidemiological studies in relatively large cohorts of patients with Klinefelter syndrome (KS) described the increased morbidity and mortality in these subjects. Our aim was to study the structure and function of arteries in different districts to investigate in these subjects possible alterations. A total of 92 patients having non-mosaic KS, diagnosed in Centre for Human Reproduction Pathology at the University of Padova, and 50 age-matched healthy male controls were studied. Klinefelter syndrome subjects and controls evaluation included complete medical history, physical examination, measurement of concentrations of the reproductive hormones, lipidic and glycidic metabolism, AR function and sensitivity, ultrasound examinations (diameters, carotid intima-media thickness and brachial flow-mediated dilation) of brachial, common carotid and common femoral artery and abdominal aorta. Klinefelter syndrome patients showed significantly reduced artery diameters in all districts evaluated. On the contrary no statistically significant difference was found in cIMT and brachial FMD values between KS patients and controls. Furthermore, we found no statistically significant correlation of artery diameters with reproductive hormones, metabolic parameters, anthropometric measures and weighted CAG repeats. To our knowledge, this is the first study finding a reduced artery diameter in several districts in KS patients compared with that of normal male subjects and overlapping to that of female subjects. We have not an explanation for this phenomenon, even if a possible involvement of genes controlling the development of vascular system might be hypothesized, and further research is required to verify this hypothesis.