Although studied for many years, there remain continued gaps in our fundamental understanding of cardiac kinematics, such as the nature and extent of heart wall volumetric changes that occur over the cardiac cycle. Such knowledge is especially important for accurate in silico simulations of cardiac pathologies and in the development of novel therapies for their treatment. A prime example is myocardial infarction (MI), which induces profound, regionally variant maladaptive remodeling of the left ventricle (LV) wall. To address this problem, we conducted an in vivo fiduciary marker-based study in an established ovine model of MI to generate detailed, time-evolving transmural in vivo volumetric measurements of LV free wall deformations in the normal state, as well as up to 12 h post-MI. This was accomplished using a transmural array of sonomicrometry crystals that acquired fiducial positions at ∼250 Hz with a positional accuracy of ∼0.1 mm, covering the entire infarct, border, and remote zones. A convex-hull method was used to directly calculate the Jacobian J(t)=Δv(t)/ΔVED from sonocrystal positions over the entire cardiac cycle, where ΔV is the volume of each convex polyhedral at end diastole (ED) (typically ∼1 cc). We demonstrated significant in vivo compressibility in normal functioning LV free wall myocardium, with JES=0.85±0.07 at end systole (ES). We also observed substantial regional variations, with the largest reduction in local myocardial tissue volume during systole in the base region accompanied by substantial transmural gradients. These patterns changed profoundly following loss of perfusion post-MI, with the apical region showing the greatest loss of volume reduction at ES. To verify that the sonocrystals did not affect local volumetric measurements, JES measures were also verified by non-invasive magnetic resonance imaging, exhibiting very similar changes in regional volume. We note that while our estimates of regional compressibility were in close agreement with the values previously reported for large animals, ranging from 5% to 20%, the direct, comprehensive measurements of wall compressibility presented herein improved on the limitations of previous reports. These limitations included dependency on the small local volumes used for analysis and often indirect measurement of compressibility. Our novel findings suggest that proper accounting for the myocardial effective compressibility at the ∼1 cc volume scale can improve the accuracy of existing kinematic indices, such as wall thickening and axial shortening, and simulations of LV remodeling following MI. Copyright © 2020 Elsevier Ltd. All rights reserved.