Among motor vehicle crashes (MVCs), little is known about whether the characteristics and collision features involving drivers with epilepsy differ from those involving drivers without any history of epilepsy. We assessed MVC features and the effect of epilepsy diagnosis on the risk of severe crash-related injuries among drivers. A total of 33 174 MVC events among people with epilepsy (PWE) and 663 480 MVC events of age- and sex-matched non-PWE (1:20) were selected. Crash-related features that involved drivers with and without epilepsy were compared, including driver eligibility, medical history of comorbidities and medications, road and environmental conditions, and accident causes. Cox and logistic regression analyses were used to examine the risks of fatality and severe injury among drivers with and without epilepsy. PWE involved in MVCs were more likely to have lower socioeconomic status, comorbidities, scooter drivers without a qualified driver's license, driving under the influence of alcohol, and be involved in single-vehicle accidents than non-PWE. Drivers with epilepsy also had a higher risk of fatality within 30 days of MVC, with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI], 1.20-1.57) and a higher risk of hospital admission within 3 days after MVC (aHR, 1.33; 95% CI, 1.29-1.38) compared to that of non-PWE. The characteristics of MVCs of drivers with epilepsy were distinct from those of non-affected drivers. And higher fatality and injury rates were observed among drivers with epilepsy, which should be considered in further policymaking regarding safe driving of PWE.