Corpus callosotomy is a palliative procedure performed to reduce the severity of drug-resistant epilepsy. The authors assessed its efficacy on different seizure types in 20 subjects (age range 5-19 years); 8 with active vagus nerve stimulator. Fifteen had complete callosotomy, 3 had anterior 2/3, and 2 had anterior 2/3 followed later by complete callosotomy. Ten had endoscopic approach. In all, 65% had ≥ 50% reduction of generalized seizures leading to falls (atonic, tonic, myoclonic); 35% became seizure-free (follow-up period: 6 months to 9 years; mean 3 years). Seizure outcome distribution was better for generalized than for partial seizures (P = .003). Endoscopic approach was as effective as transcranial approach. Seven subjects who failed vagus nerve stimulator therapy responded with ≥50% seizure reduction. Corpus callosotomy is an effective treatment for intractable generalized epilepsy leading to falls with significant seizure reduction or even elimination of seizures, in the majority of children.