Currently, there is no full three-dimensional (3D) microstructural mechanical model of coronary artery based on measured microstructure including elastin, collagen and smooth muscle cells. Many structural models employ mean values of vessel microstructure, rather than continuous distributions of microstructure, to predict the mechanical properties of blood vessels. Although some models show good agreements on macroscopic vessel responses, they result in a lower elastin stiffness and earlier collagen recruitment. Hence, a full microstructural constitutive model is required for better understanding vascular biomechanics in health and disease. Here, a 3D microstructural model that accounts for all constituent microstructure is proposed to predict macroscopic and microscopic responses of coronary arteries. Coronary artery microstructural parameters were determined based on previous statistical measurements while mechanical testing of arteries (n = 5) were performed in this study to validate the computational predictions. The proposed model not only provides predictions of active and passive stress distributions of vessel wall, but also enables reliable estimations of material parameters of individual fibers and cells and thus predicts microstructural stresses. The validated microstructural model of coronary artery sheds light on vascular biomechanics and can be extend to diseased vessels for better understanding of initiation, progression and clinical treatment of vascular disease.