Purpose To use multiparametric magnetic resonance (MR) imaging to assess for and establish age-related differences in healthy thigh muscles. Materials and Methods Ninety-five subjects (47 men, 48 women; median age, 47 years) with healthy body mass index were grouped according to age: 30-39 years (n = 25), 40-49 years (n = 25), 50-59 years (n = 25), and 60-69 years (n = 20). Multiparametric MR imaging (intravoxel incoherent motion diffusion-weighted, diffusion-tensor, multiecho Dixon, and dynamic contrast material-enhanced MR imaging) was performed at 3.0 T. Two radiologists independently evaluated parametric maps of the anterior, medial, and posterior compartments. Welch-modified one-way analysis of variance and post hoc Dunnet T3 test were used to evaluate differences in apparent diffusion, true diffusion, and pseudodiffusion coefficients; perfusion fraction; fractional anisotropy (FA); fat percentage; volume transfer constant; constant efflux rate from the extravascular-extracellular space to plasma; volume fraction of the extravascular-extracellular space (Ve); incremental area under the curve; and Pearson and Spearman correlation coefficients were used to evaluate relationship strength. Multiple regression analysis was performed to identify independent predictors of age, and interrater reliability was assessed with intraclass correlation coefficients. Results There were significant differences among the age groups in apparent diffusion coefficients (P = .010), true diffusion coefficients (P = .045), FA (P < .001), Ve (P = .029) of the anterior compartment muscles, and fat percentages of all three compartments (P ≤ .001). Moreover, FA (Pearson r = 0.428, Spearman ρ = 0.431; P < .001) and Ve (r = 0.226, P = .030 and ρ = 0.309, P = .003) in the anterior compartment and fat percentages in all three compartments (r = 0.481, 0.475, and 0.573; ρ = 0.515, 0.487, and 0.667; respectively; P < .001) were positively associated with age. Multiple regression analysis showed that age was predictive of fat percentage in the posterior compartment (β = 0.500, P < .001) and of FA in the anterior compartment (β = 0.194, P = .042). Interrater reliability was excellent (intraclass correlation coefficient, 0.745-0.992). Conclusion Multiple MR imaging parameters were significantly associated with age in thigh muscles. © RSNA, 2017 Online supplemental material is available for this article.