We assessed the effect of intra-coronary attenuation on diagnostic accuracy using 64-slice computed tomography coronary angiography (CT-CA). We enrolled 170 patients with suspected coronary artery disease who underwent conventional coronary angiography (CA) and 64-slice CT-CA (100 ml of Iomeprol 400 mg I/ml at 4 ml/s). The study population was divided into two groups (85 patients each based on median attenuation of 326 HU) based on mean arterial attenuation; group 1 with low attenuation and group 2 with high attenuation. Diagnostic accuracy for the detection of significant coronary artery stenosis was determined for both groups using CA as reference standard. Overall, 163 significant stenoses were detected in 1,030 assessable coronary artery segments in group 1 compared with 160 significant stenoses in 1,020 assessable segments in group 2. The average intra-coronary attenuation was significantly (P < 0.05) higher for group 2 (388 +/- 46 HU) compared with group 1 (291 +/- 33 HU). The corresponding sensitivity and specificity values for detection of significant coronary artery stenosis were higher for group 2 (96.3% and 97.6%, respectively) than for group 1 (82.8% and 93.2%, respectively) and were more marked in distal coronary segments than in proximal segments. Higher intra-coronary attenuation on CT-CA results in greater diagnostic accuracy for detection of coronary artery stenosis.