Autogenous veins undergo intimal hyperplasia and medial thickening when used as arterial bypass grafts. Exposing veins to arterial pressure and flow subjects them to three static deformations, three static stresses, increased pulsatile deformations, pulsatile stresses, and altered shear stress at the blood-intima interface. All of these occur simultaneously; thus it is unclear which of these nine mechanical factors predispose to the histologic changes that occur in the vein wall. Three sequential experiments were performed in 38 dogs to determine the role of each of these factors. Results showed that intimal hyperplasia is best associated with low flow velocity, a factor correlated with low blood-artery shear stress. By contrast, medial thickening is best associated with increased deformation of the vein wall in the circumferential direction (increased diameter). These findings correlate with clinical responses of vein grafts.