To refine the currently used, weight-grouped protocol for coronary computed tomography angiography (CCTA), in terms of the radiation and contrast medium dose, through clinical evaluation. Methods: Following the current routine setting that varies between three weight groups (group A: 55-65 kg, group B: 66-75 kg, group C: 76-85 kg), three additional reduction protocols were proposed to each group, with different combinations of lowered tube voltage (70-100 kVp), tube current (100-220 mAs), and iodine delivery rate (0.8-1.5 gI/s). A total of 321 patients scheduled for CCTA due to suspected coronary artery disease were enrolled, who were randomly assigned to one of the four subgroups of settings under the corresponding weight group. The resulting objective image quality was compared by measuring the contrast-to-noise ratio and signal-to-noise ratio.Subjective image quality was graded by two radiologists using a 4-point Likert scale, on a total of 3848 segments. The optimal protocol for each weight group was determined with respect to the image quality and the applied radiation dose. Results: For all three groups, no significant difference was noticed in objective images quality between subgroups of dose settings (all p > 0.05). The average score on subjective image quality was ≥3 for every subgroup, while the percentage of score 4 showed greater dependence on the setting, ranging from 83.2% to 91.5%, and was chosen to be the determining factor. The optimal dose settings were found to be 80 kVp, 150 mAs, and 1.0 gI/s for patients of 55-75 kg in weight, and 100 kVp, 170 mAs, and 1.5 gI/s for those of 76-85 kg. Conclusion: It is feasible to refine the currently used, weight-grouped protocol for CCTA in terms of radiation and contrast medium dose, by use of an optimization strategy where the balance between dose and image quality can be improved in a routine clinical setting.