Arteries often demonstrate geometric variations such as elliptic and eccentric cross sections, stenosis, and tapering along the longitudinal axis. Effects of these variations on the mechanical stability of the arterial wall have not been investigated. The objective of this study was to determine the buckling behavior of arteries with elliptic, eccentric, stenotic, and tapered cross sections. The arterial wall was modeled as a homogenous anisotropic nonlinear material. Finite element analysis was used to simulate the buckling process of these arteries under lumen pressure and axial stretch. Our results demonstrated that arteries with an oval cross section buckled in the short axis direction at lower critical pressures compared to circular arteries. Eccentric cross-sections, stenosis, and tapering also decreased the critical pressure. Stenosis led to dramatic pressure variations along the vessel and reduced the buckling pressure. In addition, tapering shifted the buckling deformation profile of the artery towards the distal end. We conclude that geometric variations reduce the critical pressure of arteries and thus make the arteries more prone to mechanical instability than circular cylindrical arteries. These results improve our understanding of the mechanical behavior of arteries.