Background: Stress myocardial perfusion imaging (MPI) is a highly valuable test in the evaluation and risk stratification of ischemic heart disease. However, negative stress MPI does not exclude coronary atherosclerosis. The Coronary artery calcium (CAC) score is a validated simple test in the evaluation of coronary atherosclerosis. Our goal was to investigate the correlation between CAC score and Duke's treadmill score, as well as the prevalence of CAC in patients with negative MPI. Methods: A total of 926 consecutive Egyptian patients, aged 30 to 60 years without known CAD, underwent CAC score testing following normal MPI. Results: In the setting of normal MPI among Egyptian patients without known CAD, mean age 48±7 years, 325 (35%) patients had a positive CAC score, and 9% had high CAC>100. Out of CAC>0, 160 were low-risk DTS. Our study showed no correlation between CAC score and DTS (P value=0.5). Age (OR=1.119, P value=<.001 and 95% confidence interval (CI)=1.071 -1.169), male gender (OR=2.795, P value=.001 and 95% (CI)=1.494 -5.230), and statin therapy (OR=2.020, P value=.008 and 95% (CI)=1.199 -3.404), were significant independent predictors of a high CAC score>100. Conclusion: In a large number of normal MPI Egyptian patients without known CAD, CAC prevalence was 35%, confirming the beneficial value of adding CAC score test to negative MPI for cardiovascular risk stratification and screening for subclinical CAD regardless of DTS. Higher CAC values and prevalence were associated with age and male gender.