Current implant materials and designs used in spinal fusion show high rates of subsidence. There is currently a need for a method to predict the mechanical properties of the endplate using clinically available tools. The purpose of this study was to develop a predictive model of the mechanical properties of the vertebral endplate at a scale relevant to the evaluation of current medical implant designs and materials. Twenty vertebrae (10 L1 and 10 L2) from 10 cadavers were studied using dual-energy X-ray absorptiometry to define bone status (normal, osteopenic, or osteoporotic) and computed tomography (CT) to study endplate thickness (μm), density (mg/mm3), and mineral density of underlying trabecular bone (mg/mm3) at discrete sites. Apparent Oliver-Pharr modulus, stiffness, maximum tolerable pressure (MTP), and Brinell hardness were measured at each site using a 3 mm spherical indenter. Predictive models were built for each measured property using various measures obtained from CT and demographic data. Stiffness showed a strong correlation between the predictive model and experimental values (r = 0.85), a polynomial model for Brinell hardness had a stronger predictive ability compared to the linear model (r = 0.82), and the modulus model showed weak predictive ability (r = 0.44), likely due the low indentation depth and the inability to image the endplate at that depth (≈0.15 mm). Osteoporosis and osteopenia were found to be the largest confounders of the measured properties, decreasing them by approximately 50%. It was confirmed that vertebral endplate mechanical properties could be predicted using CT and demographic indices.