Rats and genetically manipulated mouse models have played an important role in the exploration of molecular causes of cardiovascular diseases. However, it has not been fully investigated whether mice or rats and humans manifest similar patterns of ventricular wall motion. Although similarities in anatomy and myofiber architecture suggest that fundamental patterns of ventricular wall motion may be similar, the considerable differences in heart size, heart rate, and sarcomeric protein isoforms may yield quantitative differences in ventricular wall mechanics. To further our understanding of the basic mechanisms of myofiber contractile performance, we quantified regional and global indexes of ventricular wall motion in mice, rats, and men using magnetic resonance (MR) imaging. Both regular cine and tagged MR images at apical, midventricular, and basal levels were acquired from six male volunteers, six Fischer 344 rats, and seven C57BL/6 mice. Morphological parameters and ejection fraction were computed directly from cine images. Myocardial twist (rotation angle), torsion (net twist per unit length), circumferential strain, and normalized radial shortening were calculated by homogeneous strain analysis from tagged images. Our data show that ventricular twist was conserved among the three species, leading to a significantly smaller torsion, measured as net twist per unit length, in men. However, both circumferential strain and normalized radial shortening were the largest in male subjects. Although other parameters, such as circumferential-longitudinal shear strain, need to be evaluated, and the causes of these differences in contractile mechanics remain to be elucidated, the preservation of twist appears fundamental to cardiac function and should be considered in studies that extrapolate data from animals to humans.