The outcome of long-term vagus nerve stimulation (VNS) was evaluated in 13 Japanese patients with intractable epilepsy, all followed up for more than 4 years (48-91 months, median 56 months). VNS achieved a long-lasting and cumulative seizure-control effect in nine of 13 patients. The mean reduction of seizure frequency in the 1st to 4th year was 28%, 47%, 54%, and 63%, respectively. The percentage of patients with >60% seizure reduction in the 1st to 4th year was 15%, 46%, 54%, and 69%, respectively. One patient did not respond to the treatment at all. No patient became completely free from seizure or free from medication, but the number and/or dosage of antiepileptic drugs was reduced in five patients. Ten patients underwent exchange of the generator and continued treatment, and two patients underwent removal of the generator because of the unsatisfactory result. VNS controlled more disabling seizures earlier and more efficiently than less disabling seizures in seven patients. The cumulative reduction of seizures was partly associated with changes in the device setting toward increased stimulation. These effects were similar in patients with or without previous resective surgery. Long-term VNS therapy achieved a favorable outcome in a significant proportion of patients with intractable epilepsy.