OBJECTIVE: This study sought to examine the risk of major cardiac adverse events and death in a nationwide cohort of patients without previous comorbidity admitted for syncope. BACKGROUND: Syncope is a common clinical event, but knowledge of prognosis is not fully elucidated in healthy individuals. METHODS: Patients without previous comorbidity admitted for syncope in Denmark from 2001 to 2009 were identified in nationwide administrative registries and matched by sex and age with 5 control subjects from the Danish population. The risk of death or recurrent syncope, implantation of pacemaker or implantable cardioverter-defibrillator, and cardiovascular hospitalization were analyzed with multivariable Cox proportional hazard models. RESULTS: We identified 37,017 patients with a first-time diagnosis of syncope and 185,085 control subjects; their median age was 47 years (interquartile range, 32 to 63 years) and 47% were male. A total of 3,023 (8.2%) and 14,251 (7.1%) deaths occurred in the syncope and the control population, respectively, yielding an event rate of 14.3 per 1,000 person-years (PY) in the syncope population. Multivariable Cox regression analysis demonstrated a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.02 to 1.10), cardiovascular hospitalization event rate of 26.5 per 1,000 PY (HR: 1.74; 95% CI: 1.68 to 1.80), recurrent syncope event rate of 45.1 per 1,000, stroke event rate of 6.8 per 1,000 PY (HR: 1.35; 95% CI: 1.27 to 1.44), and pacemaker or implantable cardioverter-defibrillator event rate of 4.2 per 1,000 PY (HR: 5.52; 95% CI: 4.67 to 5.73; p <0.0001). CONCLUSIONS: The first admission for syncope among healthy individuals significantly predicts the risk of all-cause mortality, stroke, cardiovascular hospitalization, device implantation, and recurrent syncope.