OBJECTIVES: Epilepsy is one of the most frequent neurological disorders. One third of epileptic patients suffering from partial onset seizures cannot be satisfactorily controlled despite the availability of a large number of anti-epileptic drugs. The present study reports on an economic evaluation of Levetiracetam (LEV) used as an add-on therapy in refractory epileptic patients. METHODS: A cost-effectiveness analysis was done using data derived from three randomised clinical trials. A dose escalation decision model comparing LEV add-on to standard therapy alone was designed. Total treatment cost estimates were based on seizure-related costs, routine follow-up of patients, cost of adverse events as well as LEV acquisition cost. The perspective is that of the Ontario (Canada) Ministry of Health. As time horizon for the estimation of costs is one year, no discounting was applied. Treatment effectiveness was measured by the number of seizure free days gained (SFDs). Extensive sensitivity analyses were performed to test the robustness of the results, including inclusion of the costs of pre-surgical evaluation and surgery in addition to the other costs. RESULTS: Total treatment cost per patient per year was estimated at Canadian dollars (CAD) 3925 for LEV add-on and at CAD 2404 for maintenance of standard therapy - the difference was mainly related to drug acquisition costs. LEV add-on was associated with an incremental gain of 19 SFDs per patient per year. As such, the incremental cost effectiveness ratio was CAD 80.7 per seizure free day gained. When costs associated with pre-surgical evaluation and surgery were considered, the LEV add-on approach was in a dominant situation leading to cost savings of CAD 5871 per patient per year. CONCLUSIONS: This economic evaluation demonstrates that Levetiracetam add-on is a cost-effective alternative to maintenance of standard therapy for the treatment of refractory epilepsy.