Rotary blood pumps (RBPs) are currently being used as a bridge to transplantation as well as for myocardial recovery and destination therapy for patients with heart failure. Physiologic control systems for RBPs that can automatically and autonomously adjust the pump flow to match the physiologic requirement of the patient are needed to reduce human intervention and error, while improving the quality of life. Physiologic control systems for RBPs should ensure adequate perfusion while avoiding inflow occlusion via left ventricular (LV) suction for varying clinical and physical activity conditions. For RBPs used as left ventricular assist devices (LVADs), we hypothesize that maintaining a constant average pressure difference between the pulmonary vein and the aorta (deltaPa) would give rise to a physiologically adequate perfusion while avoiding LV suction. Using a mock circulatory system, we tested the performance of the control strategy of maintaining a constant average deltaPa and compared it with the results obtained when a constant average pump pressure head (deltaP) and constant rpm are maintained. The comparison was made for normal, failing, and asystolic left heart during rest and at light exercise. The deltaPa was maintained at 95 +/- 1 mm Hg for all the scenarios. The results indicate that the deltaPa control strategy maintained or restored the total flow rate to that of the physiologically normal heart during rest (3.8 L/m) and light exercise (5.4 L/m) conditions. The deltaPa approach adapted to changing exercise and clinical conditions better than the constant rpm and constant deltaP control strategies. The deltaPa control strategy requires the implantation of two pressure sensors, which may not be clinically feasible. Sensorless RBP control using the deltaPa algorithm, which can eliminate the failure prone pressure sensors, is being currently investigated.