Myocardial infarction (MI) is death and necrosis of myocardial tissue secondary to ischemia. MI is associated with adverse cardiac remodeling, progressive heart chamber dilation, ventricular wall thinning, and loss of cardiac function. Myocardial necrosis can be experimentally induced in rodents to simulate human MI by surgical occlusion of coronary arteries. When induced in knockout or transgenic mice, this model is useful for the identification of molecular modulators of cell death, cardiac remodeling, and preclinical therapeutic potential. Herein we outline in tandem, methods for microsurgical ligation of the left anterior descending artery followed by quantitation of myocardial necrosis. Necrosis is quantified after staining the heart with triphenyltetrazolium chloride.