The shear strength of human trabecular bone may influence overall bone strength under fall loading conditions and failure at bone-implant interfaces. Here, we sought to compare shear and compressive yield strengths of human trabecular bone and elucidate the underlying failure mechanisms. We analyzed 54 specimens (5-mm cubes), all aligned with the main trabecular orientation and spanning four anatomic sites, 44 different cadavers, and a wide range of bone volume fraction (0.06–0.38). Micro-CT-based non-linear finite element analysis was used to assess the compressive and shear strengths and the spatial distribution of yielded tissue;​ the tissue-level constitutive model allowed for kinematic non-linearity and yielding with strength asymmetry. We found that the computed values of both the shear and compressive strengths depended on bone volume fraction via power law relations having an exponent of 1.7 (R²=0.95 shear;​ R²=0.97 compression). The ratio of shear to compressive strengths (mean±SD, 0.44±0.16) did not depend on bone volume fraction (p=0.24) but did depend on microarchitecture, most notably the intra-trabecular standard deviation in trabecular spacing (R²=0.23, p<0.005). For shear, the main tissue-level failure mode was tensile yield of the obliquely oriented trabeculae. By contrast, for compression, specimens having low bone volume fraction failed primarily by large-deformation-related tensile yield of horizontal trabeculae and those having high bone volume failed primarily by compressive yield of vertical trabeculae. We conclude that human trabecular bone is generally much weaker in shear than compression at the apparent level, reflecting different failure mechanisms at the tissue level.