Various control and monitoring algorithms have been proposed to improve the left-ventricular assist device (LVAD) therapy by reducing the still-occurring adverse events. We developed a novel multi-objective physiological control system that relies on the pump inlet pressure (PIP). Signal-processing algorithms have been implemented to extract the required features from the PIP. These features then serve for meeting various objectives: pump flow adaptation to the perfusion requirements, aortic valve opening for a predefined time, augmentation of the aortic pulse pressure, and monitoring of the LV pre- and afterload conditions as well as the cardiac rhythm. Controllers were also implemented to ensure a safe operation and prevent LV suction, overload, and pump backflow. The performance of the control system was evaluated in vitro, under preload, afterload and contractility variations. The pump flow adapted in a physiological manner, following the preload changes, while the aortic pulse pressure yielded a threefold increase compared to a constant-speed operation. The status of the aortic valve was detected with an overall accuracy of 86% and was controlled as desired. The proposed system showed its potential for a safe physiological response to varying perfusion requirements that reduces the risk of myocardial atrophy and offers important hemodynamic indices for patient monitoring during LVAD therapy.