Objective The passive properties of the venous wall are important for the compliance function of the venous system. The objective of this study was to quantify the passive biomechanical response and structural growth and remodeling of veins subjected to chronic venous reflux and hypertension. Methods To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured in a canine model by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound was used to investigate the passive biomechanical response of both control common iliac veins (n = 9 dogs) and common iliac veins subjected to 8 weeks of venous reflux and hypertension (n = 9 dogs). The changes in vein wall thickness and constituent composition were quantified by multiphoton microscopy and histologic evaluation. Results Biomechanical results indicate that the veins became less compliant when exposed to 8 weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be associated with a significant increase in wall thickness (P < .05) and collagen-to-elastin ratio (P < .05). After 8 weeks of chronic reflux and hypertension, the circumferential vein wall stress was significantly reduced (P < .05) because of wall thickening, although it was not restored to control levels. Conclusions The growth and remodeling of the venous wall reduces the wall stress, but the stress remains higher than at baseline at 8 weeks. The compliance of the veins also decreases because of the increase in wall thickness and remodeling of the microstructure of the venous wall. These findings provide insight into potential adaptations of the venous system in reflux and hypertension.