SYNTAX score (SS) has been reported to be an independent predictor of future cardiac events including target lesion revascularization. The aim of this study was to assess the relation between SS and plaque characteristics and poststent vascular response using optical coherence tomography in coronary artery tree and left anterior descending artery (LAD) in patients with stable angina. A total of 179 lesions among 165 patients, including 100 lesions in LAD, were analyzed. Patients were stratified into tertiles. In pre–percutaneous coronary intervention analysis of whole coronary tree and LAD, lesions of the third tertile had the highest prevalence of lipid-rich plaque. Compared with the first tertile, the third tertile had greater lipid index, thinner fibrous cap, and higher prevalence of thin-cap fibroatheroma. In poststent optical coherence tomography, the incidence of stent edge dissection and irregular protrusion was higher in the third tertile compared with the first tertile in coronary tree analysis. In LAD analysis, the prevalence of irregular protrusion was the highest in the third tertile. In conclusion, high SS may reflect higher plaque vulnerability. Stent edge dissection and irregular protrusion were more frequent in patients with higher SS, indicating poor vascular response to stenting. Our results may explain higher cardiac event rate and target lesion revascularization in patients with higher SS.