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Background: Valproic acid is the drug of choice for a wide variety of epileptic seizures and syndromes because of its broad spectrum of activity and because, in most patients, it is well tolerated. Although weight gain is a well-known adverse effect of valproic acid therapy, only a few studies have addressed weight gain associated with it in children aged 2-8 years., Objective: To evaluate valproic acid-associated changes in the body mass index (BMI) z-scores and to assess changes in serum triglyceride, cholesterol, and fasting glucose levels in young children receiving valproic acid treatment., Methods: Eighty-seven patients (39 females, 48 males) receiving valproic acid therapy for at least 3 months were included in the retrospective longitudinal study. Mean +/- SD age at initiation of therapy was 4.8 +/- 0.8 years. Changes in BMI z-scores as well as serum triglyceride, total cholesterol, and fasting glucose levels were evaluated as continuous variables and analyzed by longitudinal methods for all patients., Results: The average change from baseline in BMI z-scores was 0.80 (p = 0.001) at 3.1 years of follow-up. No significant change in triglyceride, cholesterol, and serum fasting glucose levels was observed over the same period. The percentage of overweight children at baseline was 6.9% and rose to 16% by the final visit (p = 0.081)., Conclusions: Valproic acid-associated weight gain may occur in young children. However, only 16% of patients were categorized as overweight at the end of the study; this percentage overlaps the percentage of overweight healthy young Italian children. The BMI z-scores significantly increased during the first 16 months of therapy, then appeared to level off. These observations may influence clinical practice and decision-making regarding suspending the drug due to weight gain in children in whom seizure control has been achieved.