We found significant sex-based morphometric differences in the central airways of healthy men and women that were only mildly attenuated in subsets matched for lung volume. Lumen areas were significantly larger in men (∼30%–50%). Large variability (∼75%–87%) in airway bifurcation angles (60°–122°) was found irrespective of sex. The branching pattern of the right main and right upper bronchi in women (but not in men) follows two phenotypes modulated by lung volume.