Purpose/Background: Although second-generation antipsychotics are used to treat and manage symptoms for several psychiatric disorders, data about their adverse effects in developmental age are limited. The aimof this prospective observational study was to verify the cardiovascular and metabolic risk in a sample of antipsychotic-naive children/adolescent patients starting risperidone therapy. Methods: Twenty-two patients, younger than 18 years, were recruited. The assessment included anthropometric data, cardiovascular parameters, blood tests, and ultrasonographic abdominal study. Results: After an average follow-up period of 7.6 months, statistically significant increases in mean values of waist circumference, body mass index (BMI), BMI percentile, BMI z score, total cholesterol, and prolactin were found. Other cardiometabolic parameters showed an upward trend in time. Subjects in pubertal/postpubertal stage and female patients were more susceptible to developing cardiometabolic changes. Moreover, significant correlations between changes in anthropometric and several metabolic parameters were found. A tendency to change in constitution of the liver parenchyma and distribution of the abdominal fat mass with ultrasonographic abdominal study was also evident. Conclusions: In our sample, several metabolic parameters showed a sensitivity to risperidone treatment. Because most of these parameters are age dependent, metabolic syndrome criteria used for adults were inappropriate in children and adolescents. Periodic clinical and instrumental evaluations and guidelines for monitoring of any metabolic, laboratory, and instrumental complications are necessary in the perspective of even long-time second-generation antipsychotics treatment in children and adolescents.