Although continuous flow (CFVAD) and pulsatile (PVAD) ventricular assist devices (VADs) are being clinically used, their effects upon aortic blood flow as a measure of overall blood distribution remain unclear. The objective of this study was to compare the effects of CFVAD and PVAD support for ascending (AscA) and descending (DA) aorta outflow cannulation upon mean aortic blood flow and waveform morphology. Six experiments were conducted in a normal, acute calf model, in which an inflow cannula was implanted in the left ventricle apex and outflow cannulae were anastomosed to both the AscA and DA. Flow probes were placed around the pulmonary artery, pump outflow, brachiocephalic trunk, and aorta proximal and distal to the DA outflow. For each acute experiment, calves received randomly selected levels of VAD support (0-100% of cardiac output) and pump failure (VAD off and outflow cannula unclamped) for each of four randomly selected test conditions: (1) PVAD and AscA, (2) PVAD and DA, (3) CFVAD and AscA, and (4) CFVAD and DA. Regardless of pump type or support level, proximal and distal aorta mean flows were lower (p < 0.05) for DA compared with the AscA. No differences in mean aortic flows between pump types at either outflow graft location were discerned. Differences in morphologic features of blood flow waveforms between PVAD and CFVAD were observed. During simulated pump failure, retrograde aortic blood flow in both the aortic arch and DA was observed. Partial ventricular suction was also observed during the greatest levels of CFVAD support and suggested pronounced effects upon both the right and left ventricle. Collectively, these findings imply that VAD outflow location may have an important role in patient response and recovery. Investigation of the long-term pathophysiologic responses to pump type and outflow location is ongoing.