The aim of this study was to elucidate the dynamic characteristics of the Thoratec HeartMate II (HMII) and the HeartWare HVAD (HVAD) left ventricular assist devices (LVADs) under clinically representative in vitro operating conditions. The performance of the two LVADs were compared in a normothermic, human blood-filled mock circulation model under conditions of steady (nonpulsatile) flow and under simulated physiologic conditions. These experiments were repeated using 5% dextrose in order to determine its suitability as a blood analog. Under steady flow conditions, for the HMII, approximately linear inverse LVAD differential pressure (H) versus flow (Q) relationships were observed with good correspondence between the results of blood and 5% dextrose under all conditions except at a pump speed of 9000 rpm. For the HVAD, the corresponding relationships were inverse curvilinear and with good correspondence between the blood-derived and 5% dextrose-derived relationships in the flow rate range of 2-6 L/min and at pump speeds up to 3000 rpm. Under pulsatile operating conditions, for each LVAD operating at a particular pump speed, an counterclockwise loop was inscribed in the HQ domain during a simulated cardiac cycle (HQ loop); this showed that there was a variable phase relationship between LVAD differential pressure and LVAD flow. For both the HMII and HVAD, increasing pump speed was associated with a right-hand and upward shift of the HQ loop and simulation of impairment of left ventricular function was associated with a decrease in loop area. During clinical use, not only does the pressure differential across the LVAD and its flow rate vary continuously, but their phase relationship is variable. This behavior is inadequately described by the widely accepted representation of a plot of pressure differential versus flow derived under steady conditions. We conclude that the dynamic HQ loop is a more meaningful representation of clinical operating conditions than the widely accepted steady flow HQ curve.