Computed tomography-based finite element analysis represents a powerful research tool for investigating the mechanics of skeletal fractures. To provide evidence that this technique can be used to predict failure loads and fracture patterns for bone structures, we compared the observed and predicted failure behaviors of 18 midsagittal sections, 10 mm thick, cut from human vertebral bodies. The specimens were scanned by computed tomography, and finite element models were generated with use of empirically determined density-property relations to assign element-specific material properties. The specimens were loaded to failure in uniaxial compression, and the models were analyzed under matching conditions. The models provided predictions of yield load that were strongly correlated with experimentally measured values (r2 > 0.86) and were typically within 25% of measured values. Predicted stiffness values were moderately correlated with measured values, but large absolute differences existed between them. Comparisons between regions of observed fracture and of high predicted strain indicated that strain was an accurate indicator of the pattern of local fracture in more than two-thirds of the bone specimens. In addition, strain contour plots provided better indicators of local fracture than did stress plots in these heterogeneous bone structures. We conclude that computed tomography-based finite element analysis can be used successfully to predict both global and local failure behavior of simplified skeletal structures.