Animal models of myocardial infarction (MI) are widely used not only in analyses of the mechanisms but also in testing the efficacy of therapeutic strategies for the disease. It is therefore critically important but almost impossible to exactly evaluate the validity of coronary artery ligation in a mouse model of MI except by anatomic and histologic analyses. We explored a noninvasive method to estimate MI through analyses of coronary perfusion by transthoracic echocardiography in mice before and 1 day after ligation of the left anterior descending coronary artery. Transthoracic echocardiography-based cardiac function, geometry, and coronary perfusion, electrocardiographic findings, and serum troponin I levels were examined in C57BL6/J mice subjected to left anterior descending artery ligation. The histologic infarct size was confirmed by staining the heart with 2,3,5-triphenyltetrazolium chloride. Among all parameters, the postoperative hyperemic peak diastolic velocity and coronary flow reserve were most correlated with infarct size (R² = .8028 and .5825, respectively; both P < .0001). With an infarct size of 30% or greater indicating successful ligation and less than 30% indicating unsuccessful ligation, receiver operating characteristic curve analysis showed that the postoperative hyperemic peak diastolic velocity and coronary flow reserve most effectively indicated the infarct size level with optimal cutoff values of 480.16 mm/s and 1.89, respectively. Furthermore, impaired cardiac function, an eccentrically expanded left ventricle, typical pathologic electrocardiographic findings, and elevated troponin I levels were observed most often in the mice with an impaired hyperemic peak diastolic velocity and coronary flow reserve. The echocardiographic hyperemic peak diastolic velocity and coronary flow reserve can estimate the histologic infarct size in mice with coronary occlusion.