An adult skeleton has over 200 bones. Each bone has a specific function. These different functions bring different types of mechanical loadings. To ensure a healthy behavior of the bone, a throughout life process occurs on the micro-architecture of the cortical bone. This process highly depends on the stress applied on the bone. The micro-architecture is able to supply blood and nutrients into the bone matrix and acts on the bone remodeling process. The architecture is formed by vascular canals where the orientation depends on the main axis of the mechanical loading. Vascular canals of the cortical bone located in long bone diaphysis are mainly oriented along the longitudinal axis of the diaphysis. Moreover, the canal network is tortuous and several geometrical features should affect the macroscopic behavior of the bone. The novelty of this work is to use a method which accurately describes the vascular architecture of the cortical bone based on micro-computed tomography and to correlate these results with the macroscopic mechanical behavior of the cortical bone. This experimental study is based on the extraction of cortical bone samples from four cadaveric human subjects. For each human subject, left and right humeri and femurs are studied. Dumbbell-shaped bone specimens are prepared from each bone. Care was taken to preserve bone properties after extraction: a maximum of 15 days was fixed between the extraction and the mechanical testing. Samples were constantly kept hydrated and stored at 4 °C in order to avoid frost/defrost cycles. Specimens are scanned and subsequently mechanically loaded to failure. Results will show the impact of the laterality of the bone on the architecture, the impact of loading on the bone on the architecture by comparing humeral and femoral samples for each human subject and finally the impact of the architecture on the mechanical behavior of the bone.