This study compares bone composition, density, and quality in bone samples derived from seven vertebrates that are commonly used in bone research: human, dog, pig, cow, sheep, chicken, and rat. Cortical femoral bone samples were analyzed for their content of ash, collagen, extractable proteins, and insulin-like growth factor-I. These parameters were also measured in bone powder fractions that were obtained after separation of bone particles according to their density. Large interspecies differences were observed in all analyses. Of all species included in the biochemical analyses, rat bone was most different, whereas canine bone best resembled human bone. In addition, bone density and mechanical testing analyses were performed on cylindrical trabecular bone cores. Both analyses demonstrated large interspecies variations. The lowest bone density and fracture stress values were found in the human samples; porcine and canine bone best resembled these samples. The relative contribution of bone density to bone mechanical competence was largely species-dependent. Together, the data reported here suggest that interspecies differences are likely to be found in other clinical and experimental bone parameters and should therefore be considered when choosing an appropriate animal model for bone research.