To assess the prognostic value of coronary artery stenosis identification by coronary computed tomographic angiography (CCTA) for the prediction of major adverse cardiac events (MACE) in a multicenter prospective cohort study. We performed a prospective multicenter observational cohort study of symptomatic patients with suspected or known coronary artery disease (CAD) (n = 172; 57% male) undergoing CCTA in accordance to ACC/AHA Appropriateness Criteria from 4 sites in and around Paris, France, and followed for a mean duration of 22.0 ± 4.5 months (interquartile range 18–26 months). Coronary arteries by CCTA were interpreted by physicians blinded to the patient characteristics for the presence or absence obstructive (≥70% luminal diameter stenosis), as well as for plaque composition categorized as non-calcified, calcified or “mixed.” MACE was defined as death, non-fatal myocardial infarction, unstable angina or target vessel revascularization. MACE event rates were compared between patients with or without obstructive plaque and with differing plaque compositions. MACE event rates were significantly higher in patients with obstructive coronary artery stenosis by CCTA compared to those without (61.1% vs. 3.9%, P < 0.01). In patients with obstructive stenosis, mixed (83.3% vs. 25.3%, P < 0.01) and calcified (94.4% vs. 50.7%, P < 0.01) plaque presence was significantly higher than in patients without obstructive stenosis, with no differences in prevalence of non-calcified plaque (27.8% vs. 20.8%, P = NS). For MACE, the negative predictive value of no observed coronary artery plaque was 100% in the follow-up period. In this prospective multicenter study of symptomatic patients with suspected or known CAD undergoing CCTAs interpreted by imagers blinded to patient characteristics, CCTA presence of plaque severity and composition successfully identifies patients at risk for incident MACE events. Importantly, a negative CCTA portends an extremely low risk for incidence MACE.