Mechanical circulatory support (MCS) devices have become a standard therapy for heart failure (HF) patients. MCS device designs may differ by level of support, inflow and/or outflow cannulation sites, and mechanism(s) of cardiac unloading and blood flow delivery. Investigation and direct comparison of hemodynamic parameters that help characterize performance of MCS devices has been limited. We quantified cardiac and vascular hemodynamic responses for different types of MCS devices. Continuous flow (CF) left ventricular (LV) assist devices (LVAD) with LV or left atrial (LA) inlet, counterpulsation devices, percutaneous CF LVAD, and intra-aortic rotary blood pumps (IARBP) were quantified using established computer simulation and mock flow loop models. Hemodynamic data were analyzed on a beat-to-beat basis at baseline HF and over a range of MCS support. Results demonstrated that all LVAD greatly diminished vascular pulsatility (P) and LV external work (LVEW). LVAD with LA inflow provided a greater reduction in LVEW compared to LVAD with LV inflow, but at the potential risk for blood stasis/thrombosis in the LV at high support. Counterpulsation provided greater coronary flow (CoF) augmentation, but had a lower reduction in LVEW compared to partial percutaneous LVAD support. IARBP diminished LVEW, but at the expense of diminished CoF due to coronary steal. The hemodynamic benefits for each type of mechanical circulatory support system are unique and clinical decisions on device selection to maximize end organ perfusion and minimize invasiveness needs to be considered for an individual patients' presentation.