Purpose: A zero coronary calcium score (CCS) is not able to provide a definite exclusion for coronary artery disease (CAD). The goal of this study was to determine the prevalence and associated cardiovascular risk factors of CAD in patients with zero CCS. Methods: Six hundred thirteen patients with zero CCS referred to coronary calcium score analysis (CCSA) and coronary computed tomography angiography (CCTA) with suspicion of CAD were included. The descriptive, univariate, and multivariate analyses were used to determine the prevalence and predictors of CAD presence. Results: Among 613 patients, 17 patients (2.7%) have NCCP, and obstructive CAD was found in 3 patients (0.48%). Multivariate analysis revealed that male gender and older age (>50 years) were significantly associated with the presence of noncalcified coronary plaques (NCCP) (p < 0.05). The receiver operating characteristic (ROC) curve analysis showed that the male gender and older age (>50 years) model had 70.6% sensitivity and 84.2% specificity for predicting NCCP. Conclusion: A non-negligible portion of patients with zero CCS had CAD. Male gender and older age (>50 years) were independently associated with NCCP. Due to the high specificity value (84.2%) and negative predictive value (99.0%) of the male gender and older age (>50 years) model, selective use of CCTA is recommended in <50 years old female patients to avoid unnecessary radiation exposure.