Particle shape is becoming increasingly recognized as an important parameter for the development of vascular-targeted carriers (VTCs) for disease treatment and diagnosis. However, limited research exists that investigates how particle shape coupled with hemodynamics affects VTC margination (localization and adhesion). In this study, we investigate the effects of particle shape parameters (volume, aspect ratio, axis length) on the margination efficacy of targeted spheres and prolate ellipsoids (rods) to an inflamed endothelial wall from human blood flow in an in vitro model of human vasculature. Overall, particles with 2 μm equivalent spherical diameters (ESD) display higher margination than particles with either 1 μm or 500 nm ESDs. Interestingly, rod-shaped microparticles (1 μm or 2 μm ESD) with high aspect ratios display significantly improved margination compared to spheres of equal volume, particularly under high shear rates and disturbed flow profiles. Nanorods (500 nm ESD), even with high aspect ratio, do not display enhanced margination compared to that of equivalent spheres, which suggests that nanorods, like nanospheres, display minimal margination due to their inability to effectively localize to the vessel wall in the presence of RBCs.