Abstract: Objective: To compare the differences in coronary computed tomography angiography (CCTA) plaque characteristics between ischemic and non-ischemic groups and to explore qualitative and quantitative plaque features that are valuable for diagnosing myocardial ischemia. This study aimed to apply these indicators in clinical practice to identify patients with potential myocardial ischemia as early as possible. Methods: A retrospective analysis was conducted on patients with coronary heart disease who underwent invasive coronary angiography for fractional flow reserve (FFR) measurement and CCTA scanning in the cardiology department of our hospital between January 2022 and December 2024. General information was analyzed at the patient level, whereas CCTA plaque characteristics were analyzed at the vessel level. Plaque analysis was performed by two radiologists with more than five years of experience in CCTA diagnosis using semi-automatic plaque analysis software blinded to the patient groups. Results: A total of 163 patients were included in the study, with no statistically significant differences in general information between the ischemic and non-ischemic groups. A total of 253 vessels were included, with 114 vessels in the ischemic and 139 in the nonischemic vessel groups. Among the qualitative plaque characteristics, the napkin-ring sign and punctate calcification were more prevalent in the ischemic than in the nonischemic vessel group. No statistically significant differences were observed in positive remodeling and low-density plaque indicators between the two groups. Among the quantitative plaque characteristics, statistically significant differences in plaque length (PL), plaque burden (PB), minimum lumen area (MLA), minimum diameter stenosis (MDS), maximum area stenosis (MAS), and remodeling index (RI) were observed between the two groups. There were no statistically significant differences in plaque volume (PV) or edge irregularity (EI). The areas under the curve (AUCs) for diagnosing myocardial ischemia in the vascular supply areas of the plaques using PL, PB, MLA, MDS, MAS, and RI were 0.672, 0.712, 0.843, 0.830, 0.821, and 0.655, respectively. The AUC for the combined detection was 0.844, which was higher than that for any single indicator. Conclusion: CCTA plaque characteristic analysis has great potential for predicting myocardial ischemia, and the combined use of multiple quantitative plaque indicators provides higher diagnostic efficacy.