Purpose: The aim of this study was to compare image quality and mean radiation dose between two groups of patients undergoing coronary computed tomography angiography (CCTA) using a 640-slice CT scanner with two protocols with different noise level thresholds expressed as standard deviation (SD). Materials and Methods: Two-hundred and sixty-eight patients underwent a CCTA with 640 slice CT scanner. In the experimental group (135 patients), an SD 51 protocol was employed; in the control group (133 patients), an SD 33 protocol was used. Mean effective dose and image quality with both objective and subjective measures were assessed. Image quality was subjectively assessed using a five-point scoring system. Segments scoring 2, 3, and 4 were considered having diagnostic quality, while segments scoring 0 and 1 were considered having nondiagnostic quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between the two groups as well as the effective radiation dose (ED) was finally assessed. Results: Comparative analysis considering diagnostic quality (2, 3, and 4 score) and nondiagnostic (score 0 and 1) quality demonstrated that image quality of SD 51 group is not significantly lower than that of S33 group. The noise was significantly higher in the SD 51 group than in the SD 33 group (P < 0.0001). The SNR and CNR were higher in the SD 33 group than in SD 51 group (P < 0.0001). Mean effective dose was 49% lower in the SD 51 group than in SD 33 group; indeed mean effective dose was 1.43 mSv ± 0.67 in the SD 51 group while it was 2.8 mSv ± 0.57 in the SD 33 group. Conclusion: Comparative analysis shows that using a 640-slice CT with a 51 SD protocol, it is possible to reduce the mean radiation dose while maintaining good diagnostic image quality.