OBJECTIVES: Epilepsy affects about 3 million people in the United States and accounts for $17.6 billion/year in health care costs.  Many antiepileptic drugs (AEDs) are used to treat the disease, but some patients remain refractory.  We compared annual overall and epilepsy-related health care costs between refractory and stable epileptic adults. METHODS: We identified adults (age≥18years) with epilepsy requiring additional AED therapy (defined as refractory) and not requiring such therapy (stable) from the MarketScan claims database in 2007-2009.  An index date was selected during calendar year 2008: the date on which an additional AED was started for refractory patients; and convenience date for stable patients whose AED use was unchanged in the prior year.  All pharmacy and medical claims in the post-index year were used to estimate overall costs. Claims with epilepsy in any diagnosis field were used to estimate epilepsy-related costs.  Analysis of covariance was used to compare outcomes after adjusting for baseline differences between groups. RESULTS:  We identified 1536 refractory and 8571 stable patients (age range: 18-64years; 50.7% vs. 47.6% female; mean Charlson comorbidity index: 0.7 vs. 0.5). Comparing refractory vs. stable patients the total health care costs were $23,238 (SD:$42,894) versus $13,839 (SD:$31,355) per patient-year (PPY) and epilepsy-related costs were $12,399 (SD: $25,773) versus $5,511 (SD:$11,730) PPY (p<0.001).  Of epilepsy-related costs, $7,257 (SD:$25,202) versus $2,751 (SD:$11,029) PPY were medical and $5,142 (SD:$4,110) versus $2,760 (SD:$3,361) PPY for AEDs (p<0.001).  After adjusting for age, gender, region, usual care physician specialty, comorbidities and risk factors, overall costs were significantly greater in the refractory compared to stable patients: $7187 (p<0.001).   CONCLUSIONS:   Although both refractory and stable epilepsy patients have a high economic burden, the costs incurred by patients with refractory disease are significantly greater. Epilepsy-related costs comprised under 50% of total costs, suggesting a substantial burden of comorbid conditions and/or under-identification of epilepsy-related utilization.