Stroke is a leading cause of death globally and is caused by stenoses, abnormal narrowings of blood vessels. Recently, there has been an increased interest in shear-activated particle clusters for the treatment of stenosis, but there is a lack of literature investigating the impact of different stenosis geometries on particle margination. Margination refers to the movement of particles toward the blood vessel wall and is desirable for drug delivery. The current study investigated ten different geometries and their effects on margination. Microfluidic devices with a constricted area were fabricated to mimic a stenosed blood vessel with different extent of occlusion, constricted length, and eccentricity (gradualness of the constriction and expansion). Spherical fluorescent particles with a diameter of 2.11 μm were suspended in blood and tracked as they moved into, through, and out of the constricted area. A margination parameter, M, was used to quantify margination based on the particle distribution after velocity normalization. Experimental results suggested that a constriction leads to an enhanced margination, whereas an expansion is responsible for a decrease in margination. Further, margination was found to increase with increasing percent occlusion and constriction length, likely a result of higher shear rate and longer residence time, respectively. Margination decreases as the stenosis geometry becomes more gradual (eccentricity increases) with the exception of a sudden constriction/expansion geometry. The findings demonstrate the importance of geometric effects on margination and call for detailed numerical modeling and geometric characterization of the stenosed areas to fully understand the underlying physics.