Syncope may have serious consequences for traffic safety. Current clinical guideline recommendations on driving following syncope are primarily based on expert consensus. To identify whether there is excess risk of motor vehicle crashes among patients with syncope compared with the general population. Danish nationwide cohort study from January 1, 2008, to December 31, 2012. Through individual-level linkage of nationwide administrative registers, all Danish residents 18 years or older were identified. Of 4 265 301 eligible Danish residents, we identified 41 039 individuals with a first-time diagnosis of syncope from emergency department or hospital. Rate of motor vehicle crashes (including nonfatal and fatal crashes), based on multivariate Poisson regression models, using the total Danish population as reference. The 41 039 patients with syncope had a median age of 66 years (interquartile range [IQR], 47-78 years); 51.0% were women; and 34.8% had cardiovascular disease. Through a median follow-up of 2.0 years (IQR, 0.8-3.3 years), 1791 patients with syncope (4.4%) had a motor vehicle crash, 78.1% of which led to injury (n = 1398) and 0.3% to death (n = 6). The crude incidence rate of motor vehicle crashes was almost doubled among patients with syncope (20.6 per 1000 person-years; 95% CI, 19.7-21.6) compared with the general population (12.1; 95% CI, 12.0-12.1), with a rate ratio (RR) of 1.83 (95% CI, 1.74-1.91) after adjustment for age, sex, socioeconomic position, and relevant comorbidities and pharmacotherapy. Men had a relatively higher rate of motor vehicle crashes (RR, 1.91; 95% CI, 1.79-2.03) than women (RR, 1.74; 95% CI, 1.63-1.87). The excess risk of motor vehicle crashes persisted throughout the follow-up period. The 5-year crash risk following syncope was 8.2% (95% CI, 7.5%-8.8%) among the population aged 18 to 69 years compared with 5.1% (95% CI, 4.7%-5.4%) in the general population. Prior hospitalization for syncope was associated with increased risk of motor vehicle crashes throughout the follow-up period. This study suggests that syncope should be considered as one of several factors in a broad assessment of fitness to drive.