Mozart's Sonata for two pianos in D major, K.448 (Mozart K.448), has been shown to improve mental function, leading to what is known as the Mozart effect. Our previous work revealed that epileptiform discharges in children with epilepsy decreased during and immediately after listening to Mozart K.448. In this study, we evaluated the long-term effects of Mozart K.448 on children with refractory epilepsy. Eleven children with refractory epilepsy were enrolled. All of the patients were diagnosed as having had refractory epilepsy for more than 1year (range=1year to 6years 4months, mean=3years 11months) and had been receiving at least two antiepileptic drugs (AED). During the study period, they listened to Mozart K.448 once a day before bedtime for 6months. Seizure frequencies were recorded 6months before they started listening to this music and monthly during the study period. All of the patients remained on the same AEDs during the 6-month study period. Frequencies of seizures were compared before and after listening to Mozart K.448. Eight of eleven patients were seizure free (N=2) or had very good responses (N=6) after 6months of listening to Mozart K.448. The remaining three (27.3%) showed minimal or no effect (effectiveness <50%; unmodified or worsened seizure frequency). The average seizure reduction was 53.6±62.0%. There were no significant differences in seizure reduction with IQ, etiology, or gender. We conclude that Mozart K.448 should be further studied as a potential add-on therapy in the treatment of children with refractory epilepsy.