The present study evaluates the effects of the blood chamber geometry and valve types on the hemodynamic characteristics of pulsatile Ventricle Assist Devices (VAD). Three aspects of VAD design were examined: valve type, inflow-outflow conduits angle and compression mechanism. For this purpose, four 3-D VAD models were numerically simulated under physiological conditions and their hemodynamic characteristics were compared: the electrohydraulic Berlin VAD as originally designed (BVAD), the Berlin VAD with bileaflet valves (Bileaflet VAD), the Berlin VAD with expanding-only walls (EOVAD), and a dual pusher-plates VAD with inclined conduits and bioprosthetic valves (DPP-VAD). A commercial computational fluid dynamic (CFD) package was used (CFD-RC, CFD Research Cooperation, Nashville). The numerical models were validated by experimental measurements, using the continuous digital particle image velocimetry (CDPIV) method, and by numerical analysis using fluid-structure interaction (FSI). The hemodynamic properties of the four models were evaluated and compared by means of pump functionality, flow patterns, washout properties and platelets level of activation (LOA). Residence time and washout properties were found as primary factors in the estimated platelets level of activation (LOA) for particles passing through the VAD. Shear stress in the flow field or on the walls had secondary importance. Large variations in washout characteristics between the different VAD models indicate the importance of the chamber geometry on the VAD hemodynamics. Inclined conduits and bioprosthetic valves exhibited the best washout characteristics (maximal number of particles left the VAD’s chamber). The compression mechanism had a minor effect on the washout properties, but it had a major impact on the flow patterns and stagnation points in the chamber. The outcome of the present study may shed light on the role of the chamber geometry, pumping mechanism and valve type on the hemodynamics of VAD. It may also offer useful information for the design or improvement of existing or newly designed pulsating heart pumps.