Wiley Periodicals, Inc. © 2018 International League Against Epilepsy Objective: To determine the frequency of older Americans with epilepsy receiving concomitant prescriptions for antiepileptic drugs (AEDs) and non-epilepsy drugs (NEDs) which could result in significant pharmacokinetic (PK) interaction, and to assess the contributions of racial/ethnic, socioeconomic, and demographic factors. Methods: Retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries ≥67 years old in 2009 augmented for minority representation. Prevalent cases had ≥1 ICD-9 345.x or ≥2 ICD-9 780.3x, and ≥1 AED. Among them, incident cases had no seizure/epilepsy claim codes nor AEDs in preceding 365 days. Drug claims for AEDs, and for the 50 most common NEDs within +/− 60 days of the index epilepsy date were tabulated. Interacting pairs of AEDs/NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. Results: Interacting drug pairs affecting NED efficacy were found in 24.5% of incident, 39% of prevalent cases. Combinations affecting AED efficacy were found in 20.4% of incident, 29.3% of prevalent cases. Factors predicting higher interaction risk included having ≥ 1 comorbidity, being eligible for Part D low Income Subsidy, and not living in the northeastern US. Protective factors were Asian race/ethnicity, and treatment by a neurologist. Significance: A substantial portion of older epilepsy patients received NED-AED combinations that could cause important PK interactions. The lower frequency among incident vs. prevalent cases may reflect changes in prescribing practices. Avoidance of interacting AEDs is feasible for most persons because of the availability of newer drugs.