OBJECTIVE: Children with epilepsy often face complex psychosocial consequences that are not fully captured by existing patient-reported outcome (PRO) measures. The Neurology Quality of Life Measurement System "Neuro-QoL" was developed to provide a set of common PRO measures that address issues important to people with neurologic disorders. This paper reports Neuro-QoL (anxiety, depression, interaction with peers, fatigue, pain, cognitive function, stigma, and upper and lower extremity functions) validation in children with epilepsy. METHOD: Patients (aged 10-18years) diagnosed with epilepsy completed Neuro-QoL and legacy measures at time 1 (initial study visit) and 6-month follow-up. Internal consistency reliability was also evaluated. Concurrent validity was assessed by comparing Neuro-QoL measures with more established "legacy" measures of the same concepts. Clinical validity was evaluated by comparing mean Neuro-QoL scores of patients grouped by clinical anchors such as disease severity. Responsiveness of the Neuro-QoL from time 1 (initial study visit) to 6months was evaluated using self-reported change as the primary anchor. RESULTS: Sixty-one patients (mean age=13.4years; 62.3% male, 75.9% white) participated. Most patients (64.2%) had been seizure-free in the 3months prior to participation, and seizure frequency was otherwise described as follows: 17.8% daily, 13.3% weekly, 35.6% monthly, and 33.3% yearly. All patients were taking antiepileptic drugs. Patients reported better function/less symptoms compared to the reference groups. Internal consistency (alpha) coefficients ranged from 0.76 to 0.87. Patients with different seizure frequencies differed on anxiety (p<.01) and cognitive function (p<.05). Compared to patients on polytherapy, those on monotherapy had better upper extremity scores (p<.05). Compared to those with localized seizures, those experiencing generalized seizures reported worse stigma (p<.05). Depression, anxiety, lower extremity, fatigue, pain, interaction with peers, and stigma also significantly discriminated patients with different levels of quality of life (p=.05). All Neuro-QoL measures were significantly correlated with other measures assessing similar domains. Stigma was related to self-reported change in several areas of functioning but in sometimes unexpected directions. SIGNIFICANCE: The Neurology Quality of Life Measurement System is a valid and reliable assessment tool for children with epilepsy and can be used in research and clinical settings.