Physiological axial strains range between 40% and 60% in arteries, resulting in stresses significantly greater than those due to normal blood pressure or flow. To investigate the contribution of axial strain to arterial remodeling and function, porcine carotid arteries were cultured for 9 days at physiological and reduced axial stretch ratios in the presence of normotensive and hypertensive transmural pressures using ex vivo perfusion techniques. Consistent with previous in vivo studies, vessels cultured with physiological levels of axial strain and exposed to hypertensive pressure had greater mass, wall area, and outer diameter relative to those cultured at the same axial stretch ratio and normotensive pressure. Reducing the amount of axial strain resulted in mass loss and decreased cell proliferation. Culture in a hypertensive pressure environment at reduced axial strain produced arteries with greater contractility in response to norepinephrine. Arteries cultured at reduced axial strain with the MMP inhibitor GM6001 maintained their masses over culture, indicating a possible mechanism for this model of axial stretch-dependent remodeling. Though not historically considered one of the primary stimuli for remodeling, multiple linear regression analysis revealed that axial strain had an impact similar to or greater than transmural pressure on various remodeling indices (i.e., outer diameter, wall area, and wet mass) suggesting that axial strain is a primary mediator of vascular remodeling.