Objective:To characterize trends in antiseizure medication (ASM) fills and total prescription costs in people with epilepsy.Methods:This was a retrospective cohort study of beneficiaries with epilepsy (ASM, plus International Classification of Diseases codes) in a 20% random Medicare sample, with continuous Fee-For-Service coverage (Parts A, B, and D) in 2008-2018. We summed the number of pill days and costs (adjusted to 2018 dollars) per person-year for each ASM. ASMs were categorized into brand versus generic, first- versus newer-generation, and enzyme-inducers versus non-inducers.Results:There were 77,000-133,000 beneficiaries with epilepsy per year. The most common ASM was phenytoin in 2008, which shifted to levetiracetam in 2018 (2008: phenytoin 25%, levetiracetam 14%; 2018: phenytoin 9%, levetiracetam 27%). Brand name (2008: 56%; 2018: 14%), first-generation (2008: 55%; 2018: 32%), and enzyme-inducing ASMs (2008: 44%; 2018: 24%) each decreased over time as a proportion of pill days. The number of brand pill days per person-year initially decreased (e.g. 2008: 250; 2009: 121; 2010: 96), but then plateaued (2013-2018: between 66-69) given a notable increase in lacosamide pill days per person (2008: 0; 2018: 20). Total brand name costs per year initially decreased 2008-2010 (2008: $150 million; 2010: $72 million) but then increased after 2010 (2018: $256 million). In 2018 brand name ASMs represented 79% of costs despite representing only 14% of pill days, a one-year pill supply became 277% more expensive for brand name but 42% less expensive for generic medications over time (2008: brand ∼$2,800 versus generic ∼$800; 2018: brand ∼$10,700 versus generic ∼$460), and many common brand name ASMs cost approximately ten-fold more per pill day than their generic equivalents.Conclusions:First-generation and enzyme-inducing ASMs waned from 2008 to 2018. While brand name ASMs initially waned translating into lower costs and potentially higher value care, after 2010 brand name costs markedly increased due to increasing use of lacosamide plus a 277% increase in per-pill cost of brand name ASMs. Brand name ASMs represented a small minority of prescriptions, but the large majority of costs.