OBJECTIVES: To calculate and compare the incremental cost-utility ratios for standard antiepileptic drug (AED) therapy with and without adjunctive lacosamide in patients with uncontrolled partial-onset seizures. METHODS: The model simulated the treatment pathway of a hypothetical cohort of 1000 patients over 2 years from the perspectives of the National Health Service (NHS) in Scotland and the Spanish Healthcare System (SNS) in 2008. A decision tree was split into four phases of six months each during which patients can become seizure free, experience a seizure reduction (responder defined as ≥50% reduction in seizures), or withdraw due to non-response. The standard therapy arm included carbamazepine, lamotrigine, levetiracetam, topiramate, and valproate. The likelihood of being in a particular health state has been estimated from clinical data. The cost of general practitioner visits, outpatient visits, hospitalizations and emergency department visits were included. Costs and utility values attached to various health states were taken from the published literature. RESULTS: Lacosamide adjunctive therapy was associated with 6730 avoided seizures and a gain of 38 quality adjusted life-years (QALYs), compared to the standard therapy arm within the two-year timeframe. Treatment with lacosamide was associated with a cost of £113 and €107 per seizure avoided, and £20,017 and €22,771 per QALY gained versus standard therapy in Scotland and Spain, respectively. Results calculated for 6-, 12- and 18-month follow-up showed respective incremental cost-utility ratios of £23,479, £21,422 and £20,998 in Scotland, and €23,771, €20,703 and €21,778 in Spain. Using a willingness-to-pay threshold of £30,000 per QALY, 80% of the simulations in Scotland and 74.2% in Spain fell below this value after 2 years of treatment. CONCLUSIONS: Lacosamide was shown to be a cost-effective adjunctive treatment in patients with uncontrolled partial-onset epilepsy in Scotland and Spain.