Sarcopenia and osteoporosis are highly prevalent syndromes in older people, characterized by loss of muscle and bone tissue, and related to adverse outcomes. Previous reports indicate mid-thigh dual-energy X-ray absorptiometry (DXA) is well suited for the simultaneous assessment of bone, muscle, and fat mass in a single scan. Using cross-sectional clinical data and whole-body DXA images of 1322 community-dwelling adults from the Geelong Osteoporosis Study (57% women, median age 59 years), bone and lean mass were quantified in three unconventional regions of interest (ROIs): (i) a 2.6-cm-thick slice of mid-thigh, (ii) a 13-cm-thick slice of mid-thigh, and (iii) the whole thigh. Conventional indices of tissue mass were also calculated (appendicular lean mass [ALM] and bone mineral density [BMD] of lumbar spine, hip, and femoral neck). The performance of thigh ROIs in identifying osteoporosis, osteopenia, low lean mass and strength, past falls, and fractures was evaluated. All thigh regions (especially whole thigh) performed well in identifying osteoporosis (area under the receiver-operating characteristic [ROC] curve [AUC] > 0.8) and low lean mass (AUC >0.95), but they performed worse in the diagnosis of osteopenia (AUC 0.7-0.8). All thigh regions were equivalent to ALM in discrimination of poor handgrip strength, gait speed, past falls, and fractures. BMD in conventional regions was more strongly associated with past fractures than thigh ROIs. In addition to being faster and easier to quantify, mid-thigh tissue masses can be used for identifying osteoporosis and low lean mass. They are also equivalent to conventional ROIs in their associations with muscle performance, past falls, and fractures; however, further validation is required for the prediction of fractures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.