Nanoindentation has been widely used as a means to measure the micro-mechanical properties of bone and to predict the macroscopic properties. The role of indent depth and indenter tip geometry in measuring the hierarchical properties of bone tissue was explored experimentally using a range of spherical indenter tips of R=5, 25, 65, and 200 μm. Nanoindentation arrays, not targeted to fall on specific structures or locations, enabled statistical sampling of osteons within PMMA-embedded, bovine, cortical bone on a single sample to a range of maximum displacements (minimum of 100 nm and maximum of 2000 nm). Elastic finite element models were then utilized to isolate the contributions of indenter tip radius, contact area, and position within the lamellar structure in comparison to the experimental results. For a small, R=5 μm indenter tip, indentation modulus consistently increased with contact depth and increased plastic deformation, resulting in an artificial increase in elastic properties. While larger radius tips (R=25, 65, and 200 μm) did not enable evaluation of a high spatial resolution on the surface, they produced data that was representative of the lower load and contact depth measurements with the smaller tip. However the sensitivity to mechanical property variations across the 2-D surface of the material was lost with increase in indenter tip size. Correspondingly, measurement variance was also decreased as the volume contributing to the indent response represented an average of surface roughness, varying mineral content, defects, and underlying tissue type and structure.