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There is controversy about whether symptomatic population with coronary artery calcium score (CACS) of zero have coronary artery disease (CAD) and the distribution at different ages. We sought to analyze the prevalence of CAD in symptomatic patients with zero CACS, especially in different age groups. We studied patients suspected of CAD and underwent CACS scan and coronary computed tomography angiography (CTA). We included patients with CACS of zero. Clinical data was collected to achieve information on demographic characteristics and risk factors. The presence of plaque and obstructive CAD were analyzed based on coronary CTA. The association between age and the prevalence of plaque and obstructive CAD was evaluated.Overall 5514 patients (51.1% men; mean age 54.40 years) were analyzed, of whom 4120 (74.72%) with normal coronary artery, 1394 (25.28%) with plaque and 514 (9.32%) with obstructive CAD. The prevalence of plaque and obstructive CAD increased significantly with age (p < 0.001). Age was significantly associated with the risk of developing plaque and obstructive CAD in the unadjusted model and multivariate model. Taking age less than 40 as a reference, risk ratios (RRs) of prevalence of plaque increased with age in the multivariate model (RR = 2.353 for 40–50, RR = 6.489 for > 70). RRs of prevalence of obstructive CAD also increased with age in the multivariate model (RR = 2.075 for 40–50, RR = 4.102 for > 70). Quite a few CAD could occur in symptomatic patients with CACS of zero, especially in old patients. Coronary CTA was required to exclude CAD in this cohort. [ABSTRACT FROM AUTHOR]