AbstractTortuous vessels are often observed in vivo and could hinder or even disrupt blood flow to distal organs. Besides genetic and biological factors, the in vivo mechanical loading seems to play a role in the formation of tortuous vessels, but the mechanism for formation of helical vessel shape remains unclear. Accordingly, the aim of this study was to investigate the biomechanical loads that trigger the occurrence of helical buckling in blood vessels using finite element analysis. Porcine carotid arteries were modeled as thick‐walled cylindrical tubes using generalized Fung and Holzapfel‐Gasser‐Ogden constitutive models. Physiological loadings, including axial tension, lumen pressure, and axial torque, were applied. Simulations of various geometric dimensions, different constitutive models and at various levels of axial stretch ratios, lumen pressures, and twist angles were performed to identify the mechanical factors that determine the helical stability. Our results demonstrated that axial torsion can cause wringing (twist buckling) that leads to kinking or helical coiling and even looping and winding. The specific buckling patterns depend on the combination of lumen pressure, axial torque, axial tension, and the dimensions of the vessels. This study elucidates the mechanism of how blood vessels buckle under various mechanical loads and how complex mechanical loads yield helical buckling.