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Purpose: Reperfusion that follows a period of ischemia paradoxically reduces vasodilator function in humans, a phenomenon referred to as vascular ischemia-reperfusion (I/R) injury. Acute whole-body hot water immersion protects against vascular I/R injury in young healthy humans. However, the effect of acute leg heating on I/R injury is unclear. Therefore, the purpose of this study was to test the hypothesis that acute lower leg heating prevents the attenuation in macro- and microvascular dilator function following I/R injury in young healthy humans. \nMethods: Three healthy male subjects (age 25 ± 4 years; height 177 ± 10 cm; weight 86 ± 16 kg; mean ± SD) immersed their lower legs into a circulated water bath for 60 min under two thermal conditions: 1) thermoneutral immersion (~33 °C); 2) hot water immersion (~42 °C). The order of thermal conditions was randomized and counterbalanced. Macrovascular (brachial artery flow-mediated dilation) and microvascular (reactive hyperemia area under the curve) dilator function were assessed using Doppler ultrasound at three time points: 1) pre-immersion; 2) 60 min post-immersion; 3) post-I/R. Vascular I/R injury was induced by occluding brachial artery blood flow for 20 min, followed by 20 min of reperfusion. \nResults: Compared with pre-immersion (6.1 ± 0.6%), macrovascular dilator function was decreased 60 min following thermoneutral immersion (4.3 ± 0.6%; P < 0.05) and was further reduced following I/R injury (4.1 ± 0.5%; P < 0.05). In contrast, macrovascular dilator function was well maintained from pre-immersion (5.8 ± 0.6%) to 60 min post hot water immersion (5.3 ± 0.6%; P = 0.4) and following I/R injury (5.3 ± 0.6%; P = 0.4 vs. pre-immersion). Microvascular dilator function was decreased 60 min following thermoneutral immersion (pre-immersion 3.3 ± 0.1 mL mmHg-1 vs. 60 min post-immersion 2.5 ± 0.3 mL mmHg-1; P < 0.05) and tended to remain decreased following I/R injury (2.7 ± 0.4 mL mmHg-1; P = 0.1 vs. pre-immersion). However, microvascular dilator function did not differ from pre-immersion (3.1 ± 0.5 mL mmHg-1) to 60 min post hot water immersion (3.0 ± 0.3 mL mmHg-1; P = 0.7), but still tended to decrease following I/R injury (2.5 ± 0.3 mL mmHg-1; P = 0.1). \nConclusions: Taken together, acute leg heating appears to prevent the decrease in macrovascular dilator function that occurs following I/R injury in young healthy humans. Further evidence is needed to determine if acute leg heating equally protects the microvasculature following I/R injury.