Background: Low wall shear stress (LSS) is an established cause of pro-atherogenic endothelial pathophysiology, yet it has never been demonstrated in the cerebral circulation affected by intracranial atherosclerotic disease (ICAD). Noninvasive CT angiography (CTA) computational fluid dynamics (CFD) enables high-resolution investigation of detailed post-stenotic phenomena. We used all available CTA data in the SAMMPRIS trial of ICAD to detect and quantify post-stenotic LSS. Methods: CTA source images from SAMMPRIS were reconstructed in 3D followed by geometry refinements to generate a mesh of the diseased arterial lesion and adjacent segments. CFD was performed with Ansys (ICEM, Fluent), applying reference boundary conditions with k-omega turbulence and non-Newtonian modeling of the traversing blood viscosity. 3D CFD parameter maps illustrated velocity, velocity swirling and corresponding wall shear stress. Results: 144 subjects enrolled in SAMMPRIS had CTA at baseline, including 140 with CTA source images enabling CFD. Post-stenotic velocity profiles revealed vortices in all cases, quantified by swirling and turbulent kinetic energy. These luminal flow changes were adjacent to focal regions of LSS in the post-stenotic region (Figure). Conclusions: Low wall shear stress is associated with vortices of fluid flow in CTA CFD modeling of ICAD from SAMMPRIS. CTA source images may be used to noninvasively quantify LSS and model this pro-atherogenic factor in ICAD across a wide variety of lesions. Future studies should examine the related endothelial biology and potential link with plaque evolution.