The three-dimensional biomechanical behavior of the vascular wall is best described by means of strain energy functions. Significant effort has been devoted lately in the development of structure-based models of the vascular wall, which account for the individual contribution of each major structural component (elastin, collagen, and vascular smooth muscle). However, none of the currently proposed structural models succeeded in simultaneously and accurately describing both the pressure-radius and pressure-longitudinal force curves. We have hypothesized that shortcomings of the current models are, in part, due to unaccounted anisotropic properties of elastin. We extended our previously developed biomechanical model to account for elastin anisotropy. The experimental data were obtained from inflation-extension tests on facial veins of five young white New Zealand rabbits. Tests have been carried out under a fully relaxed state of smooth muscle cells for longitudinal stretch ratios ranging from 100% to 130% of the in vivo length. The experimental data (pressure-radius, pressure-force, and zero-stress-state geometries) provided a complete biaxial mechanical characterization of rabbit facial vein and served as the basis for validating the applicability and accuracy of the new biomechanical model of the venous wall. When only the pressure-radius curves were fitted, both the anisotropic and the isotropic models gave excellent results. However, when both pressure-radius and pressure-force curves are simultaneously fitted, the model with isotropic elastin shows an average weighted residual sum of squares of 8.94 and 23.9 in the outer radius and axial force, respectively, as compared to averages of 6.07 and 4.00, when anisotropic elastin is considered. Both the Alkaike information criterion and Schwartz criterion show that the model with the anisotropic elastin is more successful in predicting the data for a wide range of longitudinal stretch ratios. We conclude that anisotropic description of elastin is required for a full 3D characterization of the biomechanics of the venous wall.