The long-term effects of vagus nerve stimulation (VNS) on behaviour were studied in 19 children with Lennox-Gastaut syndrome. We used the following stimulation parameters: output current: 112 to 2mA; signal frequency: 30Hz frequency; signal pulse width: 500&mgr;s; signal 'on and off' time: 30s 'on,' 3min 'off.' The test battery consisted of cognitive tests assessing mental age and quality of life measurements assessing independency, behavioural problems, and mood. The results show relatively small changes in the behavioural outcomes, concurrent with the modest effects of VNS on seizure frequency (an average of 20.6% seizure reduction). When baseline measurements are compared with the follow-up measures, neither the cognitive measure nor the quality of life measures show any deterioration and the cognitive measure (mental age) showed mild positive changes (gain of 4.2 months mental age during the follow-up period). None of the changes were statistically significant. Treatment effect was most prominent in the group with the highest mental age at baseline, which suggests that mental retardation is a negative prognostic factor for VNS treatment. Moreover, in this specific patient group, treatment effect did not increase with treatment duration. Some evidence during follow-up suggests a direct positive effect of VNS on behavioural function, independent of changes in seizure frequency. Long-term treatment with VNS is not associated with adverse behavioural effects. Mental retardation is a negative prognostic factor for the efficacy of VNS.