Abstract Background The direct relationship between plaque rupture (PR) that cause acute coronary syndrome (ACS) and wall shear stress (WSS) remains uncertain. Methods From the Kobe University ACS-OCT registry, one hundred ACS patients whose culprit lesions had PR documented by optical coherence tomography (OCT) were enrolled. Lesion-specific 3D coronary artery models were created using OCT data. Specifically, at the ruptured portion, the tracing of the luminal edge of the residual fibrous cap was smoothly extrapolated to reconstruct the luminal contour before PR. Then, WSS was computed from computational fluid dynamics (CFD) analysis by a single core laboratory. Relationships between WSS and the location of PR were assessed with 1) longitudinal 3-mm segmental analysis and 2) circumferential analysis. In the longitudinal segmental analysis, each culprit lesion was subdivided into five 3-mm segments with respect to the minimum lumen area (MLA) location at the centered segment (Figure. 1). In the circumferential analysis, we measured WSS values at five points from PR site and non-PR site on the cross-sections with PR. Also, each ruptured plaque was categorized into the lateral type PR (L-PR), central type PR (C-PR), and others according to the relation between the site of tearing and the cavity (Figure. 2). Results In the longitudinal 3-mm segmental analysis, the incidences of PR at upstream (UP1 and 2), MLA, and downstream (DN1 and 2) were 45%, 40%, and 15%, respectively. The highest average WSS was located in UP1 in the upstream PR (UP1: 15.5 (10.4–26.3) vs. others: 6.8 (3.3–14.7) Pa, p<0.001) and MLA segment in the MLA PR (MLA: 18.8 (6.0–34.3) vs. others: 6.5 (3.1–11.8) Pa, p<0.001), and the second highest WSS was located at DN1 in the downstream PR (DN1: 5.8 (3.7–11.5) vs. others: 5.5 (3.7–16.5) Pa, p=0.035). In the circumferential analysis, the average WSS at PR site was significantly higher than that of non-PR site (18.7 (7.2–35.1) vs. 13.9 (5.2–30.3) Pa, p<0.001). The incidence of L-PR, C-PR, and others were 51%, 42%, and 7%, respectively. In the L-PR, the peak WSS was most frequently observed in the lateral site (66.7%), whereas that in the C-PR was most frequently observed in the center site (70%) (Figure. 3). In the L-PR, the peak WSS value was significantly lower (44.6 (19.6–65.2) vs. 84.7 (36.6–177.5) Pa, p<0.001), and the thickness of broken fibrous cap was significantly thinner (40 (30–50) vs. 80 (67.5–100) μm, p<0.001), and the lumen area at peak WSS site was significantly larger than those of C-PR (1.5 (1.3–2.0) vs. 1.4 (1.1–1.6) mm2, p=0.008). Multivariate analysis demonstrated that the presence of peak WSS at lateral site, thinner broken fibrous cap thickness, and larger lumen area at peak WSS site were independently associated with the development of the L-PR. Conclusions A combined approach with CFD simulation and morphological plaque evaluation by using OCT might be helpful to predict future ACS events induced by PR. Funding Acknowledgement Type of funding source: None