An experimental and computational study of screw pullout from cortical bone has been conducted. A novel modification of standard pullout tests providing real time image capture of damage mechanisms during screw pullout was developed. Pullout forces, measured using the novel test rig, have been validated against standard pullout tests. Pullout tests were conducted, considering osteon alignment, to investigate the effect of osteons aligned parallel to the axis of the orthopaedic screw (longitudinal pullout) as well as the effect of osteons aligned perpendicular to the axis of the screw (transverse pullout). Distinctive alternate failure mechanisms, for longitudinally and transversely orientated cortical bone during screw pullout, were uncovered. Vertical crack propagation, parallel to the axis of the screw, was observed for a longitudinal pullout. Horizontal crack propagation, perpendicular to the axis of the screw, was observed for a transverse pullout. Finite element simulation of screw pullout, incorporating material damage and crack propagation, was also performed. Simulations revealed that a homogenous material model for cortical bone predicts vertical crack propagation patterns for both longitudinal and transverse screw pullout. A bi-layered composite model representing cortical bone microstructure was developed. A unique set of material and damage properties was used for both transverse and longitudinal pullout simulations, with only layer orientations being changed. Simulations predicted: (i) higher pullout forces for transverse pullout; (ii) horizontal crack paths perpendicular to screw axis for transverse pullout, whereas vertical crack paths were computed for longitudinal pullout. Computed results agreed closely with experimental observations in terms of pullout force and crack propagation. (C) 2012 Elsevier Ltd. All rights reserved.