Phagocytosis after myocardial infarction (MI) is a prerequisite to cardiac repair. Recruited monocytes clear necrotic cardiomyocytes and differentiate into cardiac macrophages. Some studies have linked apoptotic cell receptors on cardiac macrophages to tissue repair; however, the contribution of precursor monocyte phagocytic receptors, which are the first to interact with the cardiac parenchyma, is unclear. The scavenger receptor cluster of differentiation (CD)36 protein was detected on cardiac Ly6cHI monocytes, and bone marrow-derived was essential for both early phagocytosis of dying cardiomyocytes and for smaller infarct sizes in female and male mice after permanent coronary ligation. deficiency led to reduced expression of phagocytosis receptor and nuclear receptor in cardiac macrophages, the latter previously shown to be required for phagocyte survival. was required for phagocytosis-induced expression, and Nr4a1 protein directly bound to gene regulatory elements. To test the overall contribution of the axis, MI was induced in double-knockout mice and led to increases in myocardial rupture. These data implicate monocyte CD36 in the mitigation of early infarct size and transition to dependent macrophage function. Increased myocardial rupture in the absence of both and underscore the physiologic significance of phagocytosis during tissue injury.-Dehn, S., Thorp, E. B. Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1-dependent mechanisms of cardiac repair.