Intra-aortic rotary blood pumps (IARBPs) have been used for partial cardiac support during cardiogenic shock, myocardial infarction, percutaneous coronary intervention, and potentially viable for long-term circulatory support. Intra-aortic rotary blood pump support continuously removes volume from the aortic root, which lowers left ventricular preload, external work (LVEW), and improves end-organ perfusion. However, IARBP support diminishes aortic root pressure and coronary artery. It may also create "coronary steal," which may produce a myocardial hypoxic state adversely affecting patient outcomes. Our objective was to develop IARBP flow modulation algorithms to eliminate coronary steal and improve the myocardial supply-demand ratio without compromising the clinical benefits of restored end-organ perfusion and reduced LVEW. The hemodynamic responses of the native ventricle, coronary, and systemic vasculature to timing and synchronization of IARBP flow modulation (cyclic variation of pump flow) were investigated using a clinical heart failure (HF) computer simulation model. A total of more than 150 combinations of varying pulse widths and time-shifts to modulate IARBP flow were tested at mean IARBP flow rates of 2, 3, and 4 L/min, and compared with HF baseline values (no IARBP support). Increasing IARBP support augmented cardiac output and diminished LVEW. Nonmodulated IARBP support significantly diminished mean diastolic coronary flow (-49%) and myocardial supply-demand ratio (-12%) compared with HF baseline. Intra-aortic rotary blood pump flow modulation increased mean diastolic coronary flow (+17%) and myocardial supply-demand ratio (+24%) compared with nonmodulated IARBP (constant flow). Modulation and synchronization of IARBP support augmented coronary artery perfusion and myocardial supply-demand ratio in simulated clinical HF while also restoring end-organ perfusion and reducing LVEW. Implementation of IARBP support with flow modulation may prevent myocardial hypoxia and improve patient outcomes. However, even with flow modulation, IARBP support provides a smaller improvement in myocardial supply demand ratio compared to ventricular assist devices and intra-aortic balloon pumps.