The angle-independent myocardial elastography, which shows good performance in our proposed theoretical framework using a three-dimensional, ultrasonic image formation model based on well-established, 3D finite-element, canine, left-ventricular models in both normal and left-circumflex ischemic cases, is employed as well as validated in vivo to assess the contractility of normal and pathological myocardia. Angle-independent myocardial elastography consists of: (1) iterative estimation of in-plane and out-of-plane cumulative displacements during systole using 1D cross-correlation and recorrelation techniques in a 2D search; (2) calculation of in-plane finite strains from the in-plane cumulative motion; and (3) computation of in-plane principal strains from the finite strains by eigen decomposition with a classification strategy. The in vivo raw data of healthy and pathological human left ventricles were acquired at 136 fps in a short-axis echocardiographic view. Similar to theory, the elastographic estimates in normal clinical cases showed radial wall thickening and circumferential shortening during systole through principal strain imaging, while those in a pathological case underwent opposite strains. The feasibility of angle-independent myocardial elastography with an automated contour tracking method was hereby demonstrated through imaging of the myocardial deformation, and principal strains were proven essential in the reliable characterization and differentiation of abnormal from normal myocardia, without any angular dependence.