OBJECTIVES: To estimate the cost-effectiveness of pregabalin and other add-on antiepileptic drug therapies in patients with refractory partial epilepsy [RPE] in Argentina METHODS: Using simulation modeling techniques, we estimated clinical outcomes and costs for a hypothetical cohort of 1000 patients with RPE alternatively assumed to receive pregabalin (300 and 600 mg/d), lamotrigine (300 and 500 mg/d), oxcarbazepine (1200 and 2400 mg/d), topiramate (200 and 400 mg/d), and no add-on therapy. Outcomes of interest were examined assuming no therapy discontinuation and included the expected mean number of days free of seizures (“seizure-free days” [SFD]) and the costs of add-on antiepileptic medication over one year for each therapy. Parameter estimates were based on efficacy data from randomized controlled trials of these agents and costs of medications (in Argentine Pesos [ARS]) from local sources. Cost-effectiveness was calculated as the incremental cost (vs no add-on therapy) per additional SFD. RESULTS: The incremental cost of pregabalin (vs no add-on therapy) per additional SFD was (mean (95% CI), ARS) 117 (91,152) for pregabalin 300 mg/d, 194 (166, 228) for lamotrigine (300 mg/d), 120 (100,150) for oxcarbazepine (2400 mg/d), and 235 (99, 1,071) for topiramate (400 mg/d). When higher dosages were examined values were 157 (132, 181) for pregabalin 600 mg/d, 306 (271, 356) for lamotrigine (500 mg/d), 176 (145, 212) for oxcarbazepine (2400 mg/d), and 196 (142, 269) for topiramate (400 mg/d). CONCLUSION: The estimated cost-effectiveness of add-on antiepileptic therapy vs no add-on therapy for patients with RPE in Argentina is favorable for pregabalin (117-157 ARS per additional SFD) followed by OXC (120-176 ARS per additional SFD).