Due to the shortage of heart donors, ventricular assist device (VAD) has been developed as a temporal or permanent cardiac support. Essentially, a continuous flow VAD is a rotary pump to maintain blood supply. In addition to hydraulic efficiency and output power, the blood damage induced by a VAD must be minimized to mitigate potential complications. It has been found in the literature that the blood damage is closely related to detailed flow field, which could only be visualized by experimental measurements and computational fluid dynamic (CFD) simulations. During the development of a VAD, CFD is widely used for optimization, and several numerical models have been proposed to estimate blood damage level. In this chapter, we demonstrated a typical study of an axial flow VAD. The physical model included a straightener, an impeller, and a diffuser, and several designs of diffuser were numerically modeled for optimization in terms of hydraulic and hemodynamic performances. To validate numerical results, experimental measurements at different regions were conducted using particle image velocimetry (PIV). It is worth noting that similar procedure would be applied to a centrifugal blood pump. Before clinical application, animal and clinical trials must be conducted to examine its actual blood damage level and other potential issues, which are valuable for next iteration of design if needed.