Computational and analytical models for the mechanical behavior of human cortical bone are used to investigate the design of orthopaedic implants and the effects of metabolic bone diseases on bone fracture susceptibility. However, the underlying structure-property relationships governing the anisotropic mechanical behavior of human cortical bone are not clear. The overall objective of this project was to investigate the hierarchical structural features governing the anisotropic elastic constants of human cortical bone tissue. X-ray diffraction was used to study the apatite crystals, microcomputed tomography was used to study the intracortical porosity, and ultrasonic wave propagation was used to measure tissue elastic constants. Apatite crystal preferred orientation was the most influential structural parameter affecting elastic anisotropy and accounted for transversely isotropic elastic symmetry in the bone extracellular matrix, exclusive of porosity. Intracortical porosity was also identified as an important structural feature affecting tissue elastic anisotropy. The volume fraction, morphology, orientation, and spatial distribution of intracortical porosity accounted for orthotropic elastic symmetry at the tissue-level due to anisotropy in the transverse plane