ABSTRACT Background: Coronary artery disease (CAD) is one of the major cardiovascular diseases. Myocardial perfusion imaging (MPI) using single photon emission computed tomography (SPECT) plays an important role in the diagnosis and prognosis of CAD. Objective: The aim of the present study was to reduce the generalization of doing calcium score for all coronary cardiac patients with negative myocardial perfusion imaging. Patients and methods: A retrospective cohort study analysis using data from Alfa Scan Center, a major outpatient radiology center in Cairo, Egypt, and conducted in Cardiology Department, Faculty of Medicine, Zagazig University that included a total sample of 1168 participants with negative myocardial perfusion imaging not known to have history of CAD, and age ranged between 20 to 80 years from both sexes. All patients were subjected for SPECT-MPI after the intravenous injection of 99mTc-sestamibi. Results: There was statistically significant difference between the two groups regarding age, gender, weight, chest pain, hypertension, dyslipidemia, diabetes, family history of CAD, beta blockers, aspirin, resting diastolic blood pressure (DBP), rest ECG abnormalities and exercise duration. Age, gender, diabetes mellitus and dyslipidemia were the predictors of any coronary artery calcification (CAC > 0) in patients with negative myocardial perfusion imaging. Age, gender and Duke Treadmill Score were the predictors of significant coronary artery calcification (CAC > 100) in patients with negative myocardial perfusion imaging. Conclusion: Calcium score for all not known coronary cardiac patients with negative MPI is a mandatory, particularly if they are old, male gender and have multiple risk factors. Keywords: Calcium Score, Coronary Arteriography, Myocardial Perfusion.