Prior multiaxial strength studies on trabecular bone have either not addressed large variations in bone volume fraction and microarchitecture, or have not addressed the full range of multiaxial stress states. Addressing these limitations, we utilized micro-computed tomography (μCT) based nonlinear finite element analysis to investigate the complete 3D multiaxial failure behavior of ten specimens (5 mm cube) of human trabecular bone, taken from three anatomic sites and spanning a wide range of bone volume fraction (0.09–0.36), mechanical anisotropy (range of E3/E1 = 3.0–12.0), and microarchitecture. We found that most of the observed variation in multiaxial strength behavior could be accounted for by normalizing the multiaxial strength by specimen-specific values of uniaxial strength (tension, compression in the longitudinal and transverse directions). Scatter between specimens was reduced further when the normalized multiaxial strength was described in strain space. The resulting multiaxial failure envelope in this normalized-strain space had a rectangular boxlike shape for normal–normal loading and either a rhomboidal boxlike shape or a triangular shape for normal-shear loading, depending on the loading direction. The finite element data were well described by a single quartic yield criterion in the 6D normalized-strain space combined with a piecewise linear yield criterion in two planes for normal-shear loading (mean error ± SD: 4.6 ± 0.8% for the finite element data versus the criterion). This multiaxial yield criterion in normalized-strain space can be used to describe the complete 3D multiaxial failure behavior of human trabecular bone across a wide range of bone volume fraction, mechanical anisotropy, and microarchitecture.