Objective-We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality. Approach and Results-Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P= 0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P= 0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.190.55; P< 0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P= 0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque. Conclusions-The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD.