OBJECTIVES: This study aims at evaluating the incremental cost-effectiveness ratio (ICER) for lacosamide compared with standard therapy alone from the perspective of the Belgian health care payer in 2010. METHODS: A decision tree simulating the treatment pathway of a hypothetical cohort of 1,000 patients over two years was split into four phases of six months each during which patients can become seizure free, experience a seizure reduction (defined as ≥50% reduction in seizures), or withdraw due to non-response. The antiepileptic drugs (AEDs) included in the standard therapy arm were extracted from the pivotal trials and included carbamazepine, lamotrigine, levetiracetam, topiramate and valproate. Health state probabilities, seizure frequency and utility values were taken from lacosamide trials or from the literature. Costs of general practitioner visits, outpatient visits, hospitalizations and emergency department visits were included. Resource use was estimated by a Belgian panel of eight neurologists. Costs were discounted at a rate of 3% and consequences at a rate of 1.5%. RESULTS: Over a 24-month period, standard AED therapy plus lacosamide led to a reduction of 7 seizures, an increase of 0.038 quality-adjusted life years, and a cost decrease of €3619 per patient as compared with standard therapy alone. Results were also calculated for a 6-, 12- and 18-month follow-up. Lacosamide plus AED therapy dominated versus standard therapy alone. Using a willingness to pay of €30,000 per quality-adjusted life year, the net monetary benefit of standard antiepileptic drug therapy plus lacosamide amounted to €4,754. The probability of standard AED therapy plus lacosamide being cost-effective was 97.3% at 6 months, 99.8% at 12 months, 99.9% at 18 months, and 100% at 24 months. CONCLUSIONS: In epileptic patients who are difficult to treat with other AEDs, standard AED therapy plus lacosamide appears to be a cost-effective alternative.