Conclusions: There is limited evidence concerning atherosclerosis screening, with mixed results on whether screening improves cardiovascular risk factors, no data on cardiovascular events, and only one study suggesting smoking cessation increased after identification of atherosclerosis determined through screening. Screening for atherosclerosis should be validated through clinical trials before widespread use is advocated. Summary: Possible noninvasive methods for screening for atherosclerosis include measurement of ultrasound-determined carotid intima-media thickness or carotid plaques, computed tomography imaging to assess for aortic calcification, ankle-brachial index, and flow-mediated brachial artery endothelial vasodilation. Indeed, there are measures of atherosclerosis that appear to improve the prediction of coronary heart disease events (O'Leary DH et al, N Engl J Med 1999;340:14-22; Fowkes FG et al, JAMA 2008;300:197-208). However, prediction of events does not necessarily lead to effective prevention of events (Lauer MS et al, N Engl J Med 2009;361:841-3; Young LH et al, JAMA 2009;301:1547-55). There is therefore significant controversy about the role of atherosclerosis screening in the routine clinical care of patients. The authors performed a systematic review to assess whether screening for atherosclerosis results in improvement in cardiovascular risk factors and in clinical outcomes. The authors searched MEDLINE and the Cochrane Clinical Trial Registry, without language restrictions, to identify studies to include in the review. Included studies were those assessing the impact of atherosclerosis screening with noninvasive imaging on cardiovascular risk factors, cardiovascular events, or mortality in adults without known cardiovascular disease. The authors identified four randomized control trials (RCT, n = 709) and eight nonrandomized studies comparing participants with evidence of atherosclerosis on screening with those without evidence of atherosclerosis (n = 2994). In the RCTs, screening for atherosclerosis did not improve cardiovascular risk factors but did seem to result in an increase in stop-smoking rates (18% vs 6%, P = .03). Nonrandomized studies found improvements in some intermediate outcomes such as an increased motivation to change lifestyle and increased perception of cardiovascular risk. Data, however, were conflicting and limited by lack of a randomized control group. No studies examined the impact of screening on cardiovascular events or death. Pooling of results was not possible because of extensive heterogeneity in screening methods and studied outcomes. Comment: Screening for atherosclerosis seems like a good idea. The unfortunate reality, however, is that there are no data to justify the expense and effort of noninvasive testing to screen for atherosclerosis. There are, in fact, no studies examining the impact of screening on cardiovascular events or death. It will be difficult to ever perform such a trial. A National Heart, Lung, and Blood Institute working group estimated that a trial on the impact of screening for atherosclerosis on clinical cardiovascular events would require >10,000 participants (http://www.nhlbi.nih.gov/meetings-workshops). Trials addressing the impact of noninvasive diagnostic techniques for screening for atherosclerosis are therefore not likely to be conducted anytime soon. Screening for atherosclerosis remains an expensive, likely low yield, and unproven concept.