OBJECTIVES: The majority of epileptic patients manage their condition with antiepileptic drugs (AEDs) to prevent seizures. Despite being adherent to AEDs, some patients fail to have adequate seizure control; therefore, they have refractory epilepsy. This study assessed the health care costs and resource utilization of epilepsy patients with partial onset seizures (POS) who were refractory compared to non-refractory patients. METHODS: Administrative claims from 2004-2008 in a US commercially insured population were analyzed. Patients aged 18-64 years were selected if they had medical claims with POS (ICD-9-CM codes: 345.4, 345.5). This study used an operational definition of 3 different AED agents dispensed as refractoriness. Patients were considered refractory from the year they received the third AED and forward.  Annual direct health care utilization and costs within each calendar year among patients who were continuously enrolled were compared between refractory and non-refractory cohorts. RESULTS: The study identified 79,149 patients with POS (mean age 33 years; 54.8% female), and 8,714 (11%) patients became refractory. In 2008, refractory patients were more likely to have a hospital admission (27.2% vs. 16.9%; p<0.001). Average annual health care costs for refractory patients were significantly higher than non-refractory patients ($33,613 vs. $19,085; p<0.001), as well as by settings for inpatient ($11,780 vs. $6,076; p<0.001), outpatient ($12,677 vs. $8,125; p<0.001) and pharmacy costs ($5,280 vs. $2,256; (p<0.001). Close to half of total costs were attributable to POS-related services. Similar trends were observed when assessing POS-related costs and utilization. The differences were consistent across calendar years examined. CONCLUSIONS: The findings from this study suggest refractoriness in epilepsy patients with POS is associated with high economic burden from the health insurer’s perspective. Refractory patients incurred 76% more healthcare costs than non-refractory patients. Improving seizure control and reducing the economic burden of refractory epilepsy remain important unmet medical needs in this population