We propose an experimental setup and protocol able to induce targeted failure of the middle vertebra in 3-segment spinal units and to capture the specimens' deformation in their post-failure state. Sixteen 3-segment spinal units with and without artificial metastases were destructively tested in axial compression using one of two failure criteria; either: (A) A clear drop in force (>10-15% of peak force) (n = 4); or (B) A minimum displacement of 5 mm (n = 12). Subsequently, the specimens were fully fixated in polymethylmethacrylate (PMMA), thereby preserving their post-failure state. Pre- and post-experiment computed tomography (CT) scans were acquired to determine the occurrence of failure in one of the vertebral bodies. All specimens were successfully fixated in their post-failure state. When applying failure criterion A, two specimens showed signs of failure. When applying failure criterion B, all specimens showed signs of failure; in 9 out of 12 specimens this occurred in the middle vertebrae only. In conclusion, this research provides an experimental setup and protocol able to induce targeted failure of 3-segment spinal units and to capture the specimens' deformation in their post-failure state. Furthermore, this study illustrates the importance of an adequate failure criterion for successful simulation of vertebral fractures in an experimental setup.