High-resolution peripheral quantitative computed tomography (HR-pQCT) quantifies bone microstructure and density at the distal tibia where there is also a sizable amount of myotendinous (muscle and tendon) tissue (M-T); however, there is no method for the quantification of M-T. This study aimed (1) to assess the feasibility of using HR-pQCT distal tibia scans to estimate M-T properties using a custom algorithm, and (2) to determine the relationship between M-T properties at the distal tibia and mid-leg muscle density (MD) obtained from pQCT. Postmenopausal women from the Hamilton cohort of the Canadian Multicenter Osteoporosis Study had a single-slice (2.3 +/- 0.5 mm) 66% site pQCT scan measuring muscle cross-sectional area (MCSA) and MD. A standard HR-pQCT scan was acquired at the distal tibia. HR-pQCT-derived M-T cross-sectional area (M(T)CSA) and M-T density (MTD) were calculated using a custom algorithm in which thresholds (34.22-194.32 mg HA/cm(3)) identified muscle seed volumes and were iteratively expanded. Pearson and Bland-Altman plots were used to assess correlations and systematic differences between pQCT- and HR-pQCT-derived muscle properties. Among 45 women (mean age: 74.6 +/- 8.5 years, body mass index: 25.9 +/- 4.3 kg/m(2)), MTD was moderately correlated with mid-leg MD across the 2 modalities (r = 0.69-0.70,p < 0.01). Bland Altman analyses revealed no evidence of directional bias for MTD-MD. HR-pQCT and pQCT measures of M(T)CSA and MCSA were moderately correlated (r = 0.44, p < 0.01). Bland-Altman plots for M(T)CSA revealed that larger MCSAs related to larger discrepancy between the distal and the mid-leg locations. This is the first study to assess the ability of HR-pQCT to measure M-T size, density, and morphometry. HR-pQCT-derived MTD was moderately correlated with mid-leg MD from pQCT. This relationship suggests that distal M-T may share common properties with muscle throughout the length of the leg. Future studies will assess the value of HR-pQCT-derived M-T properties in the context of falls, mobility, and balance.