The influence of coronary calcification on the diagnostic performance of coronary computed tomography angiography (CTA) remains controversial. This study attempts to assess the effect of coronary calcium score (CS) on the diagnostic accuracy of detecting coronary artery disease (CAD) using 64-row multidetector computed tomography (MDCT). Over a period of 2 years and 9 months, 113 symptomatic patients (37-87 year-old, mean 62.3, 92 males) underwent 64-row MDCT for coronary CS and CTA. All had conventional coronary angiography (CCA) within 90 (mean 9.6) days. Coronary CTA was evaluated with CCA as the gold standard. Of 113 patients, 18 patients had a CS of 0, 18 had scores between 1 and 100, 27 between 101 and 400, and 50 had scores >400. With respect to patient-based analysis, the accuracy of CTA was 90.3%, the sensitivity was 95%, and the specificity was 78.8%. Regarding patients with CS > 400, the accuracy, sensitivity, and specificity were 92, 95.6, and 60%, respectively. On vessel-based analysis, the specificity of CTA in different vessels with CS < [double bond] 400 and CS > 400 was as follows: right coronary artery 87.1% versus 87.5% (P = 0.924); left main artery 94.8% versus 66.7% (P = 0.173); left anterior descending artery 77.1% versus 27.3% (P = 0.001); and left circumflex artery 83.3% versus 42.8% (P = 0.011). A high CS does not significantly affect the diagnostic accuracy and sensitivity of CTA; however, it significantly decreases the specificity, particularly the left anterior descending and left circumflex arteries.