ABSTRACT Raloxifene positively affects mechanical properties of the bone matrix in part through modification of skeletal‐bound water. The goal of this study was to determine if raloxifene‐induced alterations in skeletal hydration could be measured in vivo using ultra‐short echotime magnetic resonance imaging (UTE‐MRI). Twelve skeletally mature female beagle dogs (n = 6/group) were treated for 6 months with oral doses of saline vehicle (VEH, 1 mL/kg/d) or raloxifene (RAL, 0.5 mg/kg/d). After 6 months of treatment, all animals underwent in vivo UTE‐MRI of the proximal tibial cortical bone. UTE‐MRI signal intensity versus echotime curves were analyzed by fitting a double exponential to determine the short and long relaxation times of water with the bone (dependent estimations of bound and free water, respectively). Raloxifene‐treated animals had significantly higher bound water (+14%; p = 0.05) and lower free water (–20%) compared with vehicle‐treated animals. These data provide the first evidence that drug‐induced changes in skeletal hydration can be noninvasively assessed using UTE‐MRI. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.