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Percutaneous electrical neurostimulation of dermatome T6 (PENS T6), associated with a low-caloric diet, has previously demonstrated to achieve a reduction in the appetite perception, inducing a better compliance of the prescribed diet and finally leading to a greater weight loss. Ghrelin has been hypothesized to be implicated in the effect of PENS T6. The aim of this study was to evaluate the effect of PENS T6 with hypocaloric diet on appetite, weight loss and dietary compliance, and its association with plasma ghrelin levels, in comparison with PENS T6 associated with normocaloric diet, transcutaneous electrical neurostimulation of T11-T12 (placebo) with hypocaloric diet, and only hypocaloric diet.A prospective, randomized study was performed. Patients with body mass index >25 kg/m2 were included. The subjects were randomized into 4 groups: patients undergoing PENS T6 in conjunction with a 1200 kcal/d diet (group 1). Patients undergoing PENS T6 and following a normocaloric diet (group 2), patients undergoing transcutaneous electrical neurostimulation of dermatomes in right iliac fossa (T11-T12) and following a 1200 kcal/d diet(group 3) and those patients following only a 1200 kcal/d diet (group 4).A total of 200 patients were included, 50 in each group. A significantly greater weight loss was obtained in patients following PENS T6 combined with diet, when compared with the other groups. Patients undergoing PENS T6, associated or not to hypocaloric diet, experienced appetite reduction and lower ghrelin levels, when compared with the other groups.The greater weight loss experienced in the patients undergoing PENS T6 is associated with appetite reduction and greater diet compliance. Appetite reduction is associated with ghrelin decrease.