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High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007-1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.