Postmarketing data about the effectiveness of zonisamide in childhood epilepsy was collected from 759 children with various forms of epilepsy (ages 3 months–15 years) to compare the long-term efficacy of zonisamide in the treatment of epilepsy in intellectually normal versus intellectually disabled children. The follow-up period was 6 months–3 years; 291 children (245 intellectually normal, 46 intellectually disabled) received zonisamide as monotherapy. The remaining patients received additional antiepilepsy drugs (AEDs); mean numbers of additional AEDs were 1.6 and 2.9 for intellectually normal and intellectually disabled groups, respectively. Effectiveness could not be evaluated in 30 of the 759 patients because of very rare or irregular seizure frequency. In the 729 patients evaluated, 78% of intellectually normal patients and 43% of intellectually disabled patients showed ≥50% reduction in the number of seizures ( P<0.001). Improvement rates seen in the intellectually normal group were almost the same for patients with generalized (82%) and partial (77%) epilepsies, whereas in the intellectually disabled group, the improvement rate was higher for partial (50%) than generalized (36%) epilepsies ( P<0.01). These results are consistent with the known phenomenon that intellectually disabled children are likely to have more intractable seizures than children with normal intelligence.