OBJECTIVES The purpose of this study was to characterize the hemodynamic force acting on plaque and to investigate its relationship with Lesion geometry. BACKGROUND Coronary plaque rupture occurs when plaque stress exceeds plaque strength. METHODS Computational fluid dynamics was applied to 114 Lesions (81 patients) from coronary computed tomography angiography. The axial plaque stress (APS) was computed by extracting the axial component of hemodynamic stress acting on stenotic lesions, and the axial Lesion asymmetry was assessed by the Luminal radius change over length (radius gradient ERG]). Lesions were divided into upstream-dominant (upstream RG > downstream RG) and downstream-dominant lesions (upstream RG < downstream RG) according to the RG. RESULTS Thirty-three Lesions (28.9%) showed net retrograde axial plaque force. Upstream APS Linearly increased as lesion severity increased, whereas downstream APS exhibited a concave function for lesion severity. There was a negative correlation (r = -0.274, p = 0.003) between APS and lesion Length. The pressure gradient, computed tomography-derived fractional flow reserve (FFRCT), and wall shear stress were consistently higher in upstream segments, regardless of the lesion asymmetry. However, APS was higher in the upstream segment of upstream-dominant lesions (11,371.96 +/- 5,575.14 dyne/cm(2) vs. 6,878.14 +/- 4,319.51 dyne/cm(2), p < 0.001), and in the downstream segment of downstream-dominant lesions (7,681.12 +/- 4,556.99 dyne/cm(2) vs. 11,990.55 +/- 5,556.64 dyne/cm(2), p < 0.001). Although there were no differences in FFRCT, % diameter stenosis, and wall shear stress pattern, the distribution of APS was different between upstream- and downstream-dominant Lesions. CONCLUSIONS APS uniquely characterizes the stenotic segment and has a strong relationship with Lesion geometry. Clinical application of these hemodynamic and geometric indices may be helpful to assess the future risk of plaque rupture and to determine treatment strategy for patients with coronary artery disease. (Evaluation of FFR, WSS, and TPF Using CCTA; NCT01857687) (C) 2015 by the American College of Cardiology Foundation.