Background: Myocardial infarction is an important risk factor for atrial fibrillation, but the role of subclinical atherosclerosis is unknown. This longitudinal study evaluates whether atherosclerosis affects the risk of atrial fibrillation in persons without overt coronary disease. Methods: This investigation was part of the Rotterdam Study, a population-based cohort study among persons 55 years or older. Participants with atrial fibrillation at baseline, with a history of myocardial infarction, or with angina pectoris and those who had undergone cardiac operative procedures were excluded, leaving 4407 subjects for the analyses. Baseline intima-media thickness of the common carotid artery and the presence of carotid plaques were used as indices of generalized atherosclerosis. During a median follow-up of 7.5 years, 269 cases of incident atrial fibrillation were identified. Relative risks were calculated with 95% confidence intervals, adjusted for age and sex, using the Cox proportional hazards model. Additional adjustments were made for body mass index, hypertension, systolic blood pressure, serum cholesterol level, smoking, diabetes mellitus, left ventricular hypertrophy on the electrocardiogram, and the use of cardiac medication. Results: The risk of atrial fibrillation was associated with carotid intima-media thickness (relative risk, 1.90; 95% confidence interval, 1.20-3.00, highest vs lowest quartile) and severity of carotid plaques (relative risk, 1.49; 95% confidence interval, 1.06-2.10, severe vs absence). Risk estimates were stronger in women than in men. Conclusions: Atherosclerosis in participants without manifest atherosclerotic disease is an independent risk factor for atrial fibrillation. These results suggest that aggressive treatment of asymptomatic atherosclerosis may help to prevent atrial fibrillation.