Patients with refractory seizures have higher morbidity and mortality rates, and poorer quality of life scores, than those with controlled seizures. To select an adequate therapy aimed to control seizures, decision must be based not only clinical criteria but also in cost-effectiveness evidence. The objective of this study is to analyze the cost-effectiveness of lacosamide 200 & 400 mg/d compared to lamotrigine 300 mg/d and topiramate 200 mg/d as adjunctive therapies for patients with uncontrolled partial-onset seizures in Colombia from the health system perspective. An Excel-based, tree-decision model was developed to assess the cost-effectiveness of the compared therapies. Treatment efficacy was measured using the proportion of individual with a 50% or greater reduction in seizure frequency from baseline to maintenance period. Other model parameters and adverse events rates were extracted from randomized clinical trials identified through a systematic literature review. Placebo adjustment was performed and horizon was established as the titration period plus maintenance of 12-weeks. Direct costs associated with medication, adverse events and cost related to treatment failure were considered. Medications costs were extracted from the 4316-2011 legislation and procedures' cost were obtained from the SOAT -2011 formulary. Cost effectiveness ratios were calculated and deterministic sensitivity analysis was conducted. Higher rates of responders were reported in lacosamide-400 mg(39%) followed by lacosamide-200 mg (33%), topiramate-200 mg (31%) and lamotrigine-300mg (24%). Mean cost per patient was lower in lamotrigine-300mg and lacosamide-200mg groups, ($668USD;$669USD respectively), followed by topiramate-200mg ($689USD) and lacosamide-400mg ($818USD). The cost-effectiveness ratio per responder was favorable for lacosamide-200mg and lacosamide-400mg ($2.057USD-$2086USD) followed by topiramate-200mg and lamotrigine-300mg ($2.228USD and $2748USD). The ICER for lacosamide-400mg was in all cases less than $100USD/additional responder. The economic model demonstrated that lacosamide-200mg and lacosamide-400mg are cost-effective treatments compared to lamotrigine-300mg and topiramate-200mg in patients whit uncontrolled partial-onset seizures in Colombia.