Myocardial infarction (MI) leads to cardiomyocyte loss, impaired cardiac function, and heart failure. Molecular genetic analyses of myocardium in mouse models of ischemic heart disease have provided great insight into the mechanisms of heart regeneration, which is promising for novel therapies after MI. Although biomechanical factors are considered an important aspect in cardiomyocyte proliferation, there are limited methods for mechanical assessment of the heart in the mouse MI model. This prevents further understanding the role of tissue biomechanics in cardiac regeneration. Here we report optical coherence elastography (OCE) of the mouse heart after MI. Surgical ligation of the left anterior descending coronary artery was performed to induce an infarction in the heart. Two OCE methods with assessment of the direction-dependent elastic wave propagation and the spatially resolved displacement damping provide complementary analyses of the left ventricle. In comparison with sham, the infarcted heart features a fibrotic scar region with reduced elastic wave velocity, decreased natural frequency, and less mechanical anisotropy at the tissue level at the sixth week post-MI, suggesting lower and more isotropic stiffness. Our results indicate that OCE can be utilized for nondestructive biomechanical characterization of MI in the mouse model, which could serve as a useful tool in the study of heart repair.