Although rotary blood pumps (RBPs) sustain life, blood exposure to continuous supra‐physiological shear stress induces adverse effects (e.g., thromboembolism); thus, pulsatile flow in RBPs represents a potential solution. The present study introduced pulsatile flow to the HeartWare HVAD using a custom‐built controller and compared hemocompatibility biomarkers (i.e., platelet aggregation, concentrations for ADAMTS13, von Willebrand factor (vWf), and free‐hemoglobin in plasma (pfHb), red blood cell (RBC) deformability, and RBC‐nitric oxide synthase (NOS) activity) between continuous and pulsatile flow in a blood circulation loop over 5 h. The HeartWare HVAD was operated using a custom‐built controller, at continuous speed (3282 rev/min) or in a pulsatile mode (mean speed = 3273 rev/min, amplitude = 430 rev/min, frequency = 1 Hz) to generate a blood flow rate of 5.0 L/min, HVAD differential pressure of 90 mm Hg for continuous flow and 92 mm Hg for pulsatile flow, and systolic and diastolic pressures of 121/80 mm Hg. For both flow regimes, the current study found; (i) ADP‐ and collagen‐induced platelet aggregation, and ADAMTS13 concentration significantly decreased after 5 h (P < 0.01; P < 0.05), (ii) ristocetin‐induced platelet aggregation significantly increased after 45 min (P < 0.05), (iii) vWf concentration did not significantly differ at any time point, (iv) pfHb significantly increased after 5 h (P < 0.01), (v) RBC deformability improved during the continuous flow regime (P < 0.05) but not during pulsatile flow, and (vi) RBC‐NOS activity significantly increased during continuous flow (15 min), and pulsatile flow (5 h; P < 0.05). The current study demonstrated: (i) speed modulation does not improve hemocompatibility of the HeartWare HVAD based on no observable differences being detected for routine biomarkers, and (ii) the time‐course for increased RBC‐NOS activity observed during continuous flow may have improved RBC deformability.