Flow-mediated dilation (FMD) relies on reactive hyperemia to stimulate the endothelium to release nitric oxide, causing smooth muscle relaxation. Hypercapnia also produces vasodilation, which is thought to be nitric oxide-independent. The purpose of this study was to compare and contrast the effects of hypercapnia and reactive hyperemia as stimuli for brachial artery dilation. On separate days, twenty-five participants underwent vasodilation studies via reactive hyperemia or hypercapnia (i.e. 10 mmHg increase in end-tidal carbon dioxide [PetCO2)]). During both studies changes in brachial artery diameter were recorded using continuous ultrasound imaging. Heart rate (HR) was measured throughout both tests. Resting HR (63 ± 11 versus 68 ± 14 beats min(-1), p = 0.0027) and baseline brachial artery diameter measurements (4.57 ± 1.51 versus 5.28 ± 1.86 mm, p = 0.022) were significantly different between reactive hyperemia and hypercapnia, respectively. HR at peak dilation (65 ± 11 versus 76 ± 14 beats min(-1), p < 0.0001), peak vessel dilation (8.68 ± 4.50 versus 5.28 ± 1.86%, p = 0.002), and time to peak dilation (90.8 ± 120.1 versus 658.3 ± 226.6 s, p < 0.0001) were also significantly different between reactive hyperemia and hypercapnia. The dynamics by which reactive hyperemia and hypercapnia stimulate vasodilation appear to differ. Hypercapnia produces a smaller and slower vasodilatory effect than reactive hyperemia. Further research is necessary to better understand the mechanisms of vasodilation under hypercapnic conditions.