Abstract At any point in space the material properties of the myocardium are characterized as orthotropic, that is, there are three mutually orthogonal axes along which both electrical and mechanical parameters differ. To investigate the role of spatial structural heterogeneity in an orthotropic material, electro-mechanically coupled models of the left ventricle (LV) were used. The implemented models differed in their arrangement of fibers and sheets in the myocardium, but were identical otherwise: (i) a generic homogeneous model, where a rule-based method was applied to assign fiber and sheet orientations, and (ii) a heterogeneous model, where the assignment of the orthotropic tissue structure was based on experimentally obtained fiber/sheet orientations. While both models resulted in pressure-volume loops and metrics of global mechanical function that were qualitatively and quantitatively similar and matched well with experimental data, the predicted deformations were strikingly different between these models, particularly with regard totorsion. Thus, the simulation results strongly suggest that heterogeneous structure properties are playing an important non-negligible role in LV mechanics and, consequently, should be accountedfor in computational models.