With little known regarding sex and limb-heterogeneity, we investigated vascular reactivity and ischemic reperfusion in the upper and lower extremities of 15 healthy men (26 ± 2 years) and women (23 ± 1 years). Doppler ultrasound was used to evaluate ischemic reperfusion (IR) and flow-mediated dilation (FMD) following suprasystolic cuff occlusion in both the arm (brachial artery (BA)) and the leg (popliteal artery (PA)). Cumulative IR (area under the curve (AUC)), normalized for muscle mass, revealed no sex-related differences in either limb (forearm: male: 38 ± 3 and female: 44 ± 4, lower leg: male: 12 ± 2 and female: 14 ± 2 ml/100g), while both groups revealed a greater IR per unit of arm muscle mass (AUC) compared to the lower leg (P < 0.05). The BA and PA was smaller in the females (BA: 0.31 ± 0.1; PA: 0.47 ± 0.1 cm) than males (BA: 0.41 ± 0.1; PA: 0.6 ± 0.2 cm). Absolute FMD/shear rate revealed attenuated vascular function in the PA of the females (female: 3.3 ± 0.6, male: 5.0 ± 0.8 (all x10^-6) cm / s^-1•s) and no sex difference in the BA (female: 1.2 ± 0.2 , male: 1.6 ± 0.1 (all x10^-6) cm / s^-1•s). In both sexes the PA demonstrated greater vascular reactivity than the BA. Thus, vascular reactivity in healthy young people is greater in the legs, regardless of sex, and females have similar vascular function to males in the upper extremities, but when normalized for shear rate appear to have poorer vascular function in the lower extremities.