ABSTRACT: BACKGROUND: Assessment of risk for serious cardiovascular outcome after syncope is difficult. Objectives: To determine the incidence of first syncope in primary care. To investigate the relation between syncope and serious cardiovascular (CV) outcome and serious injury. METHODS: Retrospective cohort study using data from the Intego general practice-based registration network, collecting data from 55 general practices (90 GP's). All patients with a first syncope from 1994 to 2008 were included; five participants without syncope were matched for age and gender for every patient with syncope. The main outcome measures were incidence of first syncope by age and gender and one year risk of serious CV outcome or injury after syncope. RESULTS: 2785 patients with syncope and 13909 matched patients without syncope were included. The overall incidence of a first syncope was 1.91 per 1000 person-years (95% CI 1.83-1.98). The incidence was higher in females (2.42 (95% CI 2.32-2.55) per 1000 person-years) compared to males (1.4 (95% CI 1.32-1.49) per 1000 person-years) and follows a biphasic pattern according to age: a first peak at the age of 15-24 years is followed by a sharp rise above the age of 45. One year serious outcome after syncope was recorded in 12.3% of patients. Increasing age (HR 1.04 (1.03-1.04)), CV comorbidity (HR 3.48 (95% CI 2.48-4.90) and CV risk factors (HR 1.65 (95% CI 1.24-2.18) are associated with serious outcome. Cox regression, adjusting for age, gender, CV comorbidity and risk factors, showed that syncope was an independent risk factor for serious CV outcome or injury (HR 3.99 (95% CI 3.44-4.63)). The other independent risk factors were CV comorbidity (HR 1.81 (95% CI 1.51-2.17)) and age (HR 1.03 (95% CI 1.03-1.04)). CONCLUSIONS: Incidence rate of first syncope in primary care was 1.91 per 1000 person-years. One year risk of serious outcome after syncope was 12.3%. Increasing age, CV comorbidity and risk factors are associated with serious outcome. Compared to a control group, syncope on itself is an independent risk factor for serious outcome (adjusted for age, gender, CV comorbidity and risk factors).