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To investigate the association between epilepsy and antiepileptic drugs and serious transport accidents requiring emergency care or resulting in death.We identified 29,220 individuals 18 years or older with epilepsy without cerebral palsy or intellectual disability and 267,637 matched controls using Swedish registers. This nationwide cohort was followed from 2006 to 2013 for serious transport accidents. We used Cox regression to analyze the risk of serious transport accidents between individuals with epilepsy and matched controls, and then stratified Cox regression to compare the risk during periods of medication with the risk during nonmedication period within the same individual with epilepsy. We adjusted for civil status, employment, education, living area, psychiatric disorders prior to the start of follow-up, and psychotropic medication.Compared to matched controls, individuals with epilepsy were at increased risk of serious transport accidents (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.29–1.46). There were increased risks of pedestrian accidents (HR 2.24, 95% CI 1.69–2.97), bicycle accidents (HR 1.68, 95% CI 1.49–1.89) and car accidents (HR 1.31, 95% CI 1.19–1.44). However, among patients with a diagnosis of epilepsy, use of antiepileptic drugs did not influence the risk of serious transport accidents in population-level comparisons (HR 0.97; 95% CI 0.85–1.11) or within-individual comparisons (HR 0.99; 95% CI 0.69–1.42).Serious transportation accidents were more common in individuals with epilepsy, but this risk was independent of use of antiepileptic drugs.