A novel physiological cardiac assist device (PCAD), the LEVRAM assist device, which is synchronized with the failing heart ejection, was developed to improve the failing heart systolic and diastolic functions and cardiac energetics. The PCAD uses a single short cannula, which is inserted into the beating left ventricle (LV) by means of a specially designed device. Blood is ejected from the PCAD into the LV after the opening of the aortic valve and augments the cardiac stroke work. The same amount of blood is withdrawn from the LV into the PCAD, through the same cannula, during the diastole. The study aims to test the effects of the PCAD on cardiac energetics and coronary blood flow. Adult normal sheep were anesthetized and the heart was exposed by left thoracotomy. Pressures transducers (Millar Instruments, Inc., Houston, TX) were inserted into the LV and aorta. LV volume was measured by sonocrystals (Sonometrics Corp., London, Ontario, Canada) and impedance catheter (CD Lycom, Argonstrat 116 Zoetermeer, 2718 SP The Netherlands). Flowmeters (transonic) measured the cardiac output (CO) and the coronary arteries (left anterior descending (LAD) and circumflex) flows. A thin cannula was inserted into the coronary sinus and the oxygen content of the LV and the coronary sinus were determined (AVOXimeter-1000). Pressure-volume loops, myocardial energetics, and coronary flow were measured. The displaced PCAD volume was 11 mL. Four different levels of assist were studied by changing the frequency of the assist: (1) assist beat after three successive regular beats [1:4], (2) assist every third beat [1:3], (3) alternate assist and normal beat [1:2], and (4) continuous assist [1:1]. Cardiac output (CO) and stroke volume (SV) increased proportionally with increasing frequency of assist. Systolic mechanical efficiency of the PCAD was above 90%. Simultaneously, the PCAD decreased the end-diastolic volume (EDV; diastolic unloading). The PCAD increased coronary flow and decreased cardiac arterial-venous O2 difference. We conclude that the PCAD efficiently augments CO and stroke work, decreases preload, and decreases the coronary arterial-venous O2 difference; all these may expedite cardiac reverse remodeling, and promote recovery of function and eventual easy explanation of the device.