PURPOSE: This study aims to evaluate and compare the efficacy of exogenous melatonin associated with desmopressin (dDAVP) and dietary recommendations. METHODS: A total of 189 patients were enrolled from the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of the 189 original patients, 153 children, aged between 5 and 14 years (mean age, 8.7 years) were included in the study. After clinical evaluation and a 3-month period of observation without treatment, children were assigned to receive treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months. RESULTS: After the 3 months of therapy, a desiderable response was achieved in 30 of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated with dDAVP, dietary recommendations, and melatonin. CONCLUSIONS: Although not statistically significant, the results show that the association between dDAVP treatment with dietary recommendations and melatonin could be considered a safe and effective treatment of NE. Considering that the statistically insignificant results might be due to the small sample size, the study will be continued to increase the number of subjects.