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Background: The coronary artery calcium (CAC) score can be used to increase (CAC score > 0) or decrease (CAC score = 0) the likelihood of coronary artery disease (CAD). We compared the CAC score with the pre-test probability (PTP) for CAD (low, intermediate, and high). Furthermore, we compared the CAC score with exercise electrocardiography (ECG) and compared both tests with coronary angiography., Methods and Results: We retrospectively identified patients with angina and/or dyspnea for whom CAC score was used to increase or decrease the likelihood of CAD. Of 882 patients, majority had low (45%) or intermediate (44%) PTP. Patients with higher PTP had significantly higher CAC scores (Cramer's V = 0.29, p < 0.0001). Most patients (57%) had a CAC score of zero, especially those with low (73%) and intermediate (49%) PTP. However, 20% of patients with high PTP had CAC score of zero. Higher CAC scores were observed in patients with abnormal exercise ECG, but association was weak and not significant (Cramer's V = 0.13, p = 0.08). Moreover, more than 40% of patients with an abnormal exercise ECG had CAC score of zero. Higher CAC scores were associated with more severe abnormalities on coronary angiography (Cramer's V = 0.43, p < 0.0001), whereas there was no association between results of exercise ECG and coronary angiography (Cramer's V = 0.11, p = 0.91)., Conclusion: CAC score can be used in addition to PTP to increase or decrease the likelihood of CAD, and it might be more useful than exercise ECG in the diagnostic work-up of chest pain., Competing Interests: The authors report no relationships that could be construed as a conflict of interest., (© 2023 Witvliet et al.)