PURPOSE: A vertebral fracture is the most common complication of osteoporosis, and various factors are involved in its occurrence. The purpose of this study was to investigate the role of trabecular and cortical bone microstructure on vertebral strength using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Three female cadaveric spines were investigated (average age: 80.3 years). The whole spine (T1-L4) was scanned by second-generation HR-pQCT at a voxel size of 60.7 μm. Bone microstructure analysis and micro finite element analysis were performed after excluding the upper and lower endplates and posterior elements of a total of 48 vertebrae. Correlations between trabecular and cortical bone microstructure parameters and estimated vertebral strength were analyzed by univariate and multivariate regression models. RESULTS: Cortical thickness (Ct.Th) and trabecular thickness (Tb.Th) were strongly correlated with estimated failure load on univariate analysis (r = 0.89, 0.82). Trabecular volumetric bone mineral density (Tb.vBMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and Ct.Th were correlated with estimated failure load on multivariate regression analysis. CONCLUSIONS: It was suggested that, in addition to trabecular bone (Tb.vBMD, BV/TV, Tb.N), cortical bone (Ct.Th) contributed significantly to vertebral strength in elderly women.