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Left ventricular assist device (LVAD) support unloads left ventricular (LV) pressure and volume and decreases wall stress. This study investigated the effect of systematic LVAD unloading on the 3-dimensional myocardial wall stress by employing finite element models containing layered fiber structure, active contractility, and passive stiffness. The HeartMate II^® (Thoratec, Inc., Pleasanton, CA) was used for LV unloading. The model geometries and hemodynamic conditions for baseline (BL) and LVAD support (LV_support) were acquired from the Penn State mock circulatory cardiac simulator. Myocardial wall stress of BL was compared with that of LV_support at 8,000, 9,000, 10,000 RPM, providing mean pump flow (Q _mean) of 2.6, 3.2, and 3.7 l/min, respectively. LVAD support was more effective at unloading during diastole as compared to systole. Approximately 40, 50, and 60 % of end-diastolic wall …