OBJECTIVES:  Newer antiepileptic drugs (AEDs) are associated with higher acquisition cost, better tolerability profile and comparable effectiveness with older AEDs. Our study aimed to evaluate the cost-effectiveness of newer AEDs in children with partial epilepsy. METHODS:  Data on the effectiveness and direct medical cost of partial epilepsy in children (<18 years old) were collected from the Universiti Kebangsaan Malaysia Medical Centre between January 2013 and December 2014. Effectiveness in terms of >50% seizure reduction or seizure-free events or combination of both outcomes (seizure controlled) were compared between newer AEDs (lamotrigine, levetiracetam and topiramate) and older AEDs (carbamazepine, clonazepam, phenytoin and valproate). RESULTS:  115 children were included in the study. Overall, newer AEDs used as monotherapy were associated with higher percentage of seizure reduction (median of 0.56 (0-250), 5.56 (0-200) and 0.42 (0-300) at six months, twelve months and end of study respectively) compared to older AEDs. Likewise, higher seizure reduction was achieved for newer AEDs as adjunct therapy with median of 6.67 (0-900), 1.11 (0-960), and 6.67(0-800) respectively. No significant difference in the seizure controlled (p>0.05) in both groups. Perscription of newer AEDs as monotherapy or adjunct therapy were not cost-effective considering the outcome of seizure controlled and seizure free rate. The incremental cost-effectiveness ratio (ICER) in monotherapy group was MYR 65,606.76/>50% seizure reduction (US$20,041.02) and in polytherapy group was MYR 52,706/>50% seizure reduction. Slight reduction in >50% seizure frequencies does not worth the relatively higher cost of treatment. CONCLUSIONS: The use of newer AEDs in the treatment of partial seizure in Malaysian were considered non-cost-effective alternative in controlling seizure. The results however need to be interpreted with caution, considering multiple factors that have impact on seizure outcome and no evaluation of tolerability profiles.This data may assist various stakeholders in choosing appropriate AEDs to improve quality use of medicines.