Many cardiac pathologies are reflected in abnormal myocardial deformation, accessible through magnetic resonance tagging (MRT). Interpretation of the MRT data is difficult, since the relation between pathology and deformation is not straightforward. Mathematical models of cardiac mechanics could be used to translate measured abnormalities into the underlying pathology, but, so far, they even fail to correctly simulate myocardial deformation in the healthy heart. In this study we investigated to what extent (1) our previously published three-dimensional finite element model of cardiac mechanics [Kerckhoffs, R.C.P., Bovendeerd, P.H.M., Kotte, J.C.S., Prinzen, F.W., Smits, K., Arts, T., 2003. Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: a model study. Ann. Biomed. Eng. 31, 536–547] can simulate measured cardiac deformation, and (2) discrepancies between strains in model and experiment are related to the choice of the myofiber orientation in the model. To this end, we measured midwall circumferential strain Ecc and circumferential-radial shear strain Ecr in three healthy subjects using MRT. Ecc as computed in the model agreed well with measured Ecc. Computed Ecr differed significantly from measured Ecr. The time course of Ecr was found to be very sensitive to the choice of the myofiber orientation, in particular to the choice of the transverse angle. Discrepancies between circumferential-radial shear strain in model and experiment were reduced strongly by increasing the transverse angle in the original model by 25%.