Approximately 50% of women and 25% of men will have an osteoporosis-related fracture after the age of 50, yet the micromechanical origin of these fractures remains unclear. Preventing these fractures requires an understanding of compression fracture formation in vertebral cancellous bone. The immediate research goal was to create clinically relevant (midvertebral body and endplate) fractures in three-vertebrae motion segments subject to physiologically realistic compressional loading conditions. Six three-vertebrae motion segments (five cervine, one cadaver) were potted to ensure physiologic alignment with the compressive load. A 3D microcomputed tomography (microCT) image of each motion segment was generated. The motion segments were then preconditioned and monotonically compressed until failure, as identified by a notable load drop (48–66% of peak load in this study). A second microCT image was then generated. These three-dimensional images of the cancellous bone structure were inspected after loading to qualitatively identify fracture location and type. The microCT images show that the trabeculae in the cervine specimens are oriented similarly to those in the cadaver specimen. In the cervine specimens, the peak load prior to failure is highest for the L4–L6 motion segment, and decreases for each cranially adjacent motion segment. Three motion segments formed endplate fractures and three formed midvertebral body fractures; these two fracture types correspond to clinically observed fracture modes. Examination of normalized-load versus normalized-displacement curves suggests that the size (e.g., cross-sectional area) of a vertebra is not the only factor in the mechanical response in healthy vertebral specimens. Furthermore, these normalized-load versus normalized-displacement data appear to be grouped by the fracture type. Taken together, these results show that (1) the loading protocol creates fractures that appear physiologically realistic in vertebrae, (2) cervine vertebrae fracture similarly to the cadaver specimen under these loading conditions, and (3) that the prefracture load response may predict the impending fracture mode under the loading conditions used in this study.