Objective: This study assessed the differentiation of treatment costs with newer and older antiepileptic drugs (AEDs) through its correlation with treatment effectiveness and an adverse event (AE) in pediatric patients with epilepsy (PPE). Methods: PPE on monotherapy of AEDs for the last 6 months were screened for this study. Seizure frequency during the study was compared with that within 6 months before the study. The following parameters were also assessed: quality of life in epilepsy, Pittsburgh Sleep Quality Index, and Liverpool AEs Profile. An incremental cost-effectiveness ratio (ICER) analysis based on the costs of pharmacotherapy was also performed. Results: Out of 80 PPE, 67 completed the study, and 13 PPE were lost after failing to meet the inclusion criteria. A total of 56.71% of PPE were on newer AEDs, and 43.28% were on older AEDs. Newer and older AEDs did not differ significantly in seizure frequency reduction and quality of life parameters, although these were improved significantly during the study period. As per ICER, newer AEDs need an additional EUR 36.82 per unit reduction in seizure frequency. Conclusion: Newer AEDs have comparatively better efficacy, although not significantly better than older AEDs. However, the additional cost per unit improvement is quite high with newer AEDs, necessitating pharmacoeconomic consideration in pediatric epilepsy treatment.