Aims Since atherosclerosis is a systemic process, risk prediction would benefit from targeting multiple components of cardiovascular disease simultaneously. To this end, it is useful to examine the predictive value of non-invasive measures of atherosclerosis in various vascular beds for both coronary heart disease (CHD) and cerebrovascular disease. Methods and results Between September 2003 and February 2006, 2153 asymptomatic participants (69.6 +/- 6.6 years) from the Rotterdam Study underwent a multi-detector computed tomography scan. During a median follow-up of 3.5 years, 58 CHD events (myocardial infarction and CHD death) and 52 cerebrovascular events (TIA and stroke) occurred. Participants were classified into low (< 5%), intermediate (5-10%), and high (> 10%) 5-year risk categories based on a refitted Framingham risk model. The model was extended by coronary, aortic arch, or carotid calcium and reclassification percentages were calculated. For the outcome CHD, the C-statistic improved from 0.693 for the Framingham refitted model to 0.743, 0.740, and 0.749 by addition of coronary, aortic arch, and carotid calcium, respectively. Reclassification was most substantial in the intermediate risk group where addition of coronary calcium reclassified 56% of persons [net reclassification improvement (NRI): 15%; P < 0.01)]. Adding aortic arch calcium led to a reclassification of 32% of persons (NRI: 8%; P = 0.01) and adding carotid calcium reclassified 51% (NRI: 9%; P = 0.02). In contrast, calcification in any of the three vascular beds did not improve cerebrovascular risk prediction. Conclusion Coronary, aortic arch, and carotid artery calcification significantly improved risk prediction of CHD but not of cerebrovascular events.