Anisotropic damage initiation criteria were developed for extended finite element method (XFEM) prediction of crack initiation and propagation in cortical bone. This anisotropic damage model was shown to accurately predict the dependence of crack propagation patterns and fracture toughness on mode mixity and on osteon orientations, as observed experimentally. Four initiation criteria were developed to define crack trajectories relative to osteon orientations and max principal stress for single and mixed mode fracture. Alternate failure strengths for tensile and compressive loading were defined to simulate the asymmetric failure of cortical bone. The dependence of cortical bone elasticity and failure properties on osteon orientation is analogous to the dependence of composite properties on fibre orientation. Hence, three of the criteria developed in the present study were based upon the Hashin damage criteria. The fourth criterion developed was defined in terms of the max principal stress. This criterion initiated off axis crack growth perpendicular to the direction of the max principal stress. The unique set of parameters calibrated accurately predicted;​ (i) the relationship between fracture energy and osteon alignment, (ii) the alternate crack patterns for both varying osteon orientations and loading angle. Application of the developed anisotropic damage models to cortical bone screw pullout highlights the potential application for orthopaedic device design evaluation.