Ischemia-reperfusion (I/R) injury is a primary cause of poor outcomes following ischemic cardiovascular events. We tested whether acute hot water immersion protects against forearm vascular I/R. METHODS: Ten (5 male, 5 female) young (23±2 years), healthy subjects participated in two trials in random order 7-21 days apart, involving: 1) 60-min of seated rest (control), or 2) 60-min of immersion in 40.5°C water (peak rectal temperature: 38.9±0.2°C). I/R was achieved 70 min following each intervention by inflating an upper arm cuff to 250mmHg for 20-min followed by 20-min of reperfusion. Brachial artery flow-mediated dilation (FMD) and forearm post-occlusive reactive hyperemia (RH) were measured as markers of macro- and micro-vascular function at three time points: 1) pre-intervention, 2) 60-min post-intervention, and 3) post-I/R. RESULTS: Neither time control nor hot water immersion alone affected FMD (both p>0.99). I/R reduced FMD from 7.4±0.7 to 5.4±0.6% (p=0.03) and this reduction was prevented following hot water immersion (7.0±0.7 to 7.7±1.0%; p>0.99). I/R also impaired RH (peak vascular conductance: 2.6±0.5 to 2.0±4mL•min^-1•mmHg^-1, p=0.003), resulting in a reduced shear stimulus (SRAUC/10^-3 : 22.5±2.4 to 16.9±2.4, p=0.04). The post-I/R reduction in peak RH was prevented by hot water immersion (2.5±0.4 to 2.3±0.4mL•min^-1•mmHg^-1; p=0.33). CONCLUSIONS: We observed a decline in brachial artery dilator function post-I/R, which may be (partly) related to damage incurred downstream in the microvasculature, as indicated by impaired RH and shear stimulus. Hot water immersion was protective against reductions in FMD and RH post-I/R, suggesting heat stress induces vascular changes consistent with reducing I/R injury following ischemic events.