Purpose To evaluate determinants of hip fracture by assessing soft-tissue composition of the upper thigh at CT. Materials and Methods In this retrospective analysis of prospectively collected data, CT studies in 55 female control participants (mean age, 73.1 years ± 9.3 [standard deviation]) were compared with those in 40 female patients (mean age, 80.2 years ± 11.0) with acute hip fractures. Eighty-seven descriptors of the soft-tissue composition were determined. A multivariable best subsets analysis was used to extract parameters best associated with hip fracture. Results were adjusted for age, height, and weight. Results of soft-tissue parameters were compared with bone mineral density (BMD) and cortical bone thickness. Areas under the receiver operating characteristic curve (AUCs) adjusted for multiple comparisons were determined to discriminate fracture. Results The hip fracture group was characterized by lower BMD, lower cortical thickness, lower relative adipose tissue volume of the upper thigh, and higher extramyocellular lipid (EML) surface density. The relative volume of adipose tissue combined with EML surface density (model S1) was associated with hip fracture (AUC, 0.85; 95% confidence interval [CI]: 0.78, 0.93), as well as trochanteric trabecular BMD combined with neck cortical thickness (model B2) (AUC, 0.84; 95% CI: 0.75, 0.92). The model including all four parameters provided significantly better (P < .01) discrimination (AUC, 0.92; 95% CI: 0.86, 0.97) than model S1 or B2. Conclusion In addition to bone mineral density and geometry of the proximal femur, the amount of adipose tissue of the upper thigh and the distribution of the adipocytes in the muscles are significantly associated with acute hip fracture at CT. © RSNA, 2018 Online supplemental material is available for this article.