We studied the clinical efficacy and tolerability, neuropsychological effects, and cost-effectiveness (direct medical costs, direct nonmedical costs, and indirect costs) of vagus nerve stimulation (VNS) in children with Lennox-like syndrome (n = 16). The situation 6 months before implantation of the device is compared with that 6 months after surgery. Seizure frequency and severity are significantly reduced during VNS: 25% of the patients show a reduction in seizure frequency of 50% or greater; overall seizure reduction is 26.9%. Measures of neuropsychological outcome show a moderate improvement in mental functioning, behavior, and mood. The scores for mood and mental age improve independently of seizure control. Side effects are minor and transient. There is a significant reduction in direct non-health care costs, ergotherapy, and the number of days of sub-optimal functioning of the child. The costs during the 6 postoperative months are 2,876.06 Euros less than the costs during the 6 months before VNS; the payback period is 2.3 years.