This study evaluated the potential effect of antiepileptic drug (AED) nonadherence on the risk of subsequent seizure. Retrospective insurance claims from the United States were analyzed. Inclusion criteria were: age 21-64 years, diagnosis of epilepsy or nonfebrile convulsions, 2 AED prescriptions, and insurance enrollment for 6 months pre- and 60 days post-AED initiation. Seizure was defined as a hospital or emergency admission associated with epilepsy or nonfebrile convulsions. Observation began 7 days post-drug initiation, ending with the first of the following: seizure, insurance disenrollment, or 365 days post-drug initiation. Adherence was measured using the medication possession ratio (MPR), with MPR <0.8 defining nonadherence. Seizure risk was assessed using an extended Cox proportional hazards model. Of 18,073 subjects identified, 2467 (14%) had 1 seizure. Mean follow-up was 133 days among subjects with event and 305 days for patients without event. Seizure risk was 21% higher among nonadherers (hazard ratio=1.205, P=0.0002) than adherers.