Acute β-adrenergic blockade increases aortic wave reflection; however, the mechanisms remain unclear. Evidence suggests that β-adrenergic receptor sensitivity in the peripheral vasculature differs between sexes. Therefore, the goal of this study was to examine whether β-adrenergic blockade alters aortic wave reflection to a similar extent in young men and women. In 31 subjects (16 men and 15 women; 26±1 years) noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and during systemic β-blockade (0.25 mg/kg bolus, followed by 0.004 mg/kg per minute of continuous infusion of propranolol). β-Blockade increased aortic augmentation index and wave reflection amplitude (aortic augmented pressure) in both sexes (P<0.01). Although the increase in augmentation index was not significantly different between sexes (7.5±1.1% versus 4.6±1.5%; P=0.07), the increase in aortic augmented pressure was greater in women compared with men (2.8±0.5 versus 1.4±0.5 mm Hg; P<0.05). Aortic augmentation index adjusted for a heart rate of 75 bp increased in women (4.1±1.1%; P<0.05) after β-blockade, whereas it was unchanged in men (0.6±1.3%; P=0.33). Moreover, the change in aortic augmentation index was inversely associated with the change in heart rate only in men (r=-0.54; P<0.05). Our data suggest that aortic wave reflection is increased to a greater extent in women after systemic β-blockade, and enhanced aortic wave reflection appears to be mediated by a reduced heart rate in men, whereas the mechanism is unclear in women.