OBJECTIVES: Epilepsy is one of the most common chronic neurological disorders in the world; therefore it is associated with substantial use of medical resources in health institutions. Approximately 60% of patients with epilepsy suffer from partial-onset seizures (POS), and among these, an estimated 30% have refractory disease. The objective of this study was to analyze the cost-effectiveness of lacosamide (LCM), a newer anti-epileptic drug (AED), versus second generation AEDs in patients with refractory POS. METHODS: We conducted an economic evaluation, using lamotrigine (LTG) 300 mg/day and topiramate (TPM) 200 mg/day as comparators for LCM 200 and 400 mg/day. The perspective was the Mexican Social Security Institute, in accordance with Mexican guidelines for Economic Evaluations. The model included the cost of drug acquisition and management of adverse events (AE) during the titration and 12 weeks of maintenance. Resource use associated with AEs was defined according to the information gathered in a Delphi Panel. The efficacy measure was the ≥50% responder rate; i.e., the percentage of patients who showed a ≥50% decrease in seizure frequency from baseline. An indirect comparison was made. RESULTS: The adjusted response rates were 33% for LCM 200 mg/day (34% unadjusted), 39% LCM 400 mg/day (41% unadjusted), 24% for LTG (20% unadjusted) and 31% for TPM (27% unadjusted). Costs per patient considering the adjustment was MX$6,872, $7,836, $6,954 and $6,485 for LCM 200 mg, LCM 400 mg, LTG and TPM, respectively. The cost per responder was lower for LCM 200 and 400 mg/day ($20,825 and $20,093, respectively) than TPM and LTG ($20,918 and $28,974, respectively). Considering unadjusted data, LCM 200 and 400 mg/day had greater differential in costs per responder compared with TPM or LTG. CONCLUSIONS: From a Mexican perspective, lacosamide represents a cost-effective treatment option for patients with POS. Sponsored by UCB.