AIMS: Considerable inter-individual variability in the efficacy of valproic acid (VPA) has been reported, with approximately 20-45% of patients failing to achieve satisfactory seizure control after VPA monotherapy. The aim of this study was to investigate the influence of non-genetic and genetic factors on 12-month VPA-response in a cohort of 194 pediatric patients. MATERIALS & METHODS: Trough concentrations were determined, and a panel of 48 variants located in pharmacokinetic and pharmacodynamic gene were genotyped. RESULTS: Aetiology was highlighted as a significant factor for the response to VPA. Specifically, patients with idiopathic epilepsy demonstrated poorer 12-month outcomes ( CONCLUSION: Our study indicated that