This study evaluated the effect of topiramate (TPM) on the quality of life (QOL) in childhood epilepsy, using the Korean quality of life in childhood epilepsy (K-QOLCE) questionnaire. An open label, prospective, observational study of the families of 664 children with epilepsy from 41 centers was conducted. The parents completed the K-QOLCE at the baseline visit and again 6months after starting TPM treatment. The parents reported the seizure frequency at both assessment dates. Statistically significant improvements in all K-QOLCE domains except social functioning were found at 6months after starting TPM treatment from the baseline-scores (P<0.05). However, improved QOL scores were not dependent on the reduction in seizure frequency. TPM significantly improved QOL in children with epilepsy, suggesting its potential clinical benefits.