Abstract Background Through the development of CT equipment and proper preparation before CT scanning, the accuracy of Coronary computed tomography angiography (CCTA) diagnosis of ischemic heart disease (IHD) is improving, and the role of CCTA in treatment decision is gradually expanding. The latest guidelines recommend CCTA as Class IIa to evaluate stent patency and native vessels in patients with chronic coronary disease. However, diagnostic performance of CCTA to evaluate stent patency in patients who underwent coronary stent was not clarified, respectively the role of CCTA in the evaluation of IHD in native coronary artery was established.. Purpose In the present study, we evaluate the agreement between CCTA and CAG in assessing stent patency in patients with de novo ischemic chest pain who underwent percutaneous coronary intervention (PCI) and evaluated which factors contribute to the differences. Methods From January 1, 2010 to December 31, 2020, we analyzed 845 patients who underwent new CCTA and CAG sequentially for the evaluation of chest pain previously underwent PCI. In CAG and CCTA, ISR is equally defined as a stenosis greater than 50% of the vessel diameter of within the stented segment or its edge (5-mm segments adjacent to the stent). The degree of In-stent restenosis was analyzed by an independently by quantitative coronary angiography (QCA). Results A total of 208 stents were analyzed, the pooled sensitivity and specificity for CCTA on the diagnosis of ISR were 0.78 (0.65-0.89) and 0.93 (0.88-0.96), respectively. LR+ and LR- were 11.19 (6.22-20.15) and 0.23 (0.14-0.39). As a result of analyzing the ISR diagnostic agreement of CCTA by dividing into ACS and CCD group, the agreement of CCTA for ISR diagnosis was relatively low in the ACS group (Sensitivity 0.69 (0.48-0.86) vs. 0.88 (0.69-0.97), specificity 0.92 (0.84-0.97) vs. 0.94 (0.86-0.98), LR+ 9 (4-20.24) vs. 13.9 (5.88-32.88), LR- 0.33 (0.19-0.6) vs. 0.13 (0.04-0.37)) (Table 1). As a result of analyzing related factors in cases of discrepancy in ISR diagnosis, the degree of stenosis in both ACS and CCD groups was mostly intermediate stenosis, which often required additional clinical evaluation (Figure 1). Conclusion When new ischemic chest pain occurred in a patient who previously underwent PCI, the diagnostic accuracy of ISR by CCTA differed depending on the patient’s IHD category. In the CCD group, the diagnostic usefulness of CCTA was comparable both native vessels and ISR, but not in the ACS group. As majority of ISR diagnostic discrepancies were in intermediate lesions, even in the ACS group, CCTA may be considered as a diagnostic tool.