Rational design of blood-wetted devices requires a careful consideration of shear-induced trauma and activation of blood elements. Critical levels of shear exposure may be established in vitro through the use of devices specifically designed to prescribe both the magnitude and duration of shear exposure. However, it is exceptionally difficult to create a homogeneous shear-exposure history by conventional means. This study was undertaken to develop a Blood Shearing Instrument (BSI) with an optimized flow path which localized shear exposure within a rotating outer ring and a stationary conical spindle. By adjustment of the rotational speed and the gap dimension, the BSI is designed to generate shear stress magnitudes up to 1500 Pa for exposure time between 0.0015 and 0.20 s with a pressure drop of 100 mm Hg. Computational fluid dynamics (CFD) revealed that a flow path designed by first-order analysis and intuition exhibited unfavorable pressure gradient, vortices, and undesirable regions of reverse flow. An optimized design was evolved utilizing a parameterized geometric model and automatic mesh generation to eliminate vortices and reversal flow and to avoid unfavorable pressure gradients. Analysis of the flow and shear fields for the extreme limits of the shear gap demonstrated an improvement in homogeneity due to shape optimization and the limitations of an annular shear device for achieving completely uniform shear exposure.