The finite element (FE) method based on high-resolution peripheral quantitative computed tomography (HR-pQCT) use a variety of tissue constitutive properties and boundary conditions at different laboratories making comparison of mechanical properties difficult. Furthermore, the advent of a second-generation HR-pQCT poses challenges due to improved resolution and a larger region of interest (ROI). This study addresses the need to harmonize results across FE models. The aims are to establish the relationship between FE results as a function of boundary conditions and a range of tissue properties for the first-generation HR-pQCT system, and to determine appropriate model parameters for the second-generation HR-pQCT system. We implemented common boundary conditions and tissue properties on a large cohort (N = 1371), and showed the relationships were highly linear (R² > 0.99) for yield strength and reaction force between FE models. Cadaver radii measured on both generation HR-pQCT with matched ROIs were used to back-calculate a tissue modulus that accounts for the increased resolution (61 µm versus 82 µm), resulting in a modulus of 8748 MPa for second-generation HR-pQCT to produce bone yield strength and reaction force equivalent to using 6829 MPa for first-generation HR-pQCT. Finally, in vivo scans (N = 61) conducted on both generations demonstrated that the larger ROI in the second-generation system results in stronger bone outcome measures, suggesting it is not advisable to convert FE results across HR-pQCT generations without matching ROIs. Together, these findings harmonize FE results by providing a means to compare findings with different boundary conditions and tissue properties, and across scanner generations.