Distensibility of the large elastic arteries is a key index for cardiovascular health. Distensibility, usually estimated from resting values in humans, is not a static characteristic, but a negative curvilinear function of pressure. We hypothesized that differences in vascular function with gender and age may only be recognized if distensibility is quantified over a range of pressures. We used isometric handgrip exercise to induce progressive increases in pressures and carotid diameters to enhance characterization of distensibility. In 30 volunteers, distributed evenly by gender and age across the third to fifth decades of life, we derived pulsatile distensibility slope as a function of arterial pressure for a dynamic distensibility index and compared it to a traditional static index at a reference pressure of 95 mmHg. We also assessed intima-media (IM) thickness. We found that women had greater dynamic distensibility within each decade, despite comparable IM thickness. Furthermore, declines in dynamic distensibility with increasing age were correlated to increased IM thickness. The static distensibility index failed to show gender-related differences in distensibility, but did show age-related differences. Our results indicate that gender- and age-related differences can be manifest even in young, healthy adults, and may only be identified with techniques that assess carotid distensibility across a range of pressures.