Cortical bone is an inhomogeneous and anisotropic tissue subjected to large loads during typical daily activities. While studies assuming isotropic material properties are frequent, anisotropy and inhomogeneity of cortical bone have been rarely taken into account. Moreover, the question, whether an assumption of anisotropy and inhomogeneity has an impact in the mechanical analysis of cortical bone, has not been explored in the literature. This study explores the relevance of anisotropy in human cortical bone. The cortical bone model has been divided into six radial regions and a different set of orthotropic material properties has been assigned to each region. This inhomogeneous and anisotropic elastic tibia model has been compared with a corresponding isotropic model under various loading modes using the finite element method. In particular, the variation in the maximum von Mises stress and strain values has been observed along the bone axis. We have observed that the isotropic model may overestimate the maximum von Mises strain up to 15% under pure compression and underestimate up to 50% under pure torsion relative to the inhomogeneous-anisotropic model. Our results suggest that consideration of anisotropy and inhomogeneity of the bone may make a significant difference in the predicted maximum von Mises strain values, which can be important for strain-based damage accumulation studies and fracture risk evaluation.