The primary purpose of this study was to determine the accuracy of tibial cortical thickness measurements derived from peripheral quantitative computed tomography (pQCT) with analysis based on the circular ring model, using high-resolution peripheral quantitative computed tomography (HR-pQCT) (isotopic voxel size of 82 μm) as a gold standard. The secondary objective was to evaluate whether the accuracy of the pQCT-based estimates of cortical thickness (CTh), cortical area (CoA), cortical density (CDen), and total area (TotA) improve with alterations of voxel size from the standard 0.5-0.2mm. Fifteen dry tibia specimens were immersed in saline in a sealed cylinder and scanned 22.5mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT yielded higher values for CTh and CDen and lower values for CoA. The differences between imaging techniques increased as the average CTh increased. No systematic bias was observed for CDen, CoA, and TotA. Similar differences were found between pQCT with voxel size 0.2mm and HR-pQCT. Significant correlations were observed for CTh (R=0.97, p ≤ 0.0001), CDen (R=0.99, p ≤ 0.0001), CoA (R=0.98, p ≤ 0.0001), and TotA (R=1.0, p ≤ 0.0001) when pQCT- and HR-pQCT-derived values were compared irrespective of which voxel size was used. Measurement variability between the imaging techniques was evident. Future studies aimed at examining cortical structure with pQCT should note that there are differences between the 2 techniques.