Background and Aims: Recent findings from our group in native Sherpas and Bolivian highlanders have identified that life-long exposure to high altitude hypoxia is associated with a reduction in flow-mediated vasodilation (FMD) (Bailey et al., 2013; Lewis et al., 2014). This would suggest that the acute reduction in vascular endothelial function is arguably an adaptive as opposed to a maladaptive response. To confirm this, the present study was designed to examine if the diminution in FMD during acute hypoxia persists over the course of acclimatisation in native lowlanders.Methods: Twelve apparently healthy young adult lowlanders aged 27 (mean) ± 7 (SD) years were enrolled into this study. A 10 MHz multifrequency linear array probe attached to a high-resolution ultrasound machine (Acuson P50, Siemens) was used to image the brachial artery and FMD was assessed according to international guidelines (Black et al., 2008). Following a 10-min resting period, the occluding cuff was placed distal to the ultrasound probe. The test consisted of a 1-min baseline, followed by a 5-min cuff inflation (>250mmHg) and a final 5-min recording post cuff deflation. Diameter and flow were recorded continuously throughout the test with a focus on the 1-min pre inflation cuff baseline and following deflation. Data were analysed using an automated edge-detection and wall-tacking software (Brachial Tools, Medical Imaging Application). Following confirmation of distribution normality using Shapiro-Wilk W tests, data were analysed with a one-way repeated measures ANOVA and post-hoc Bonferroni-corrected paired samples t-tests. Data are expressed as mean ± SD.Results: Hypoxia did not alter baseline or peak flow and diameter or the reactive hyperaemic response. In contrast, FMD decreased from 9.7 ± 4.8 % to 7.7 ± 4.1 % during acute hypoxia, which persisted during chronic hypoxia (5.6 ± 2.5 %, P < 0.05 vs. normoxia). Likewise, the time to peak diameter was prolonged (normoxia = 42 ± 10 sec; acute hypoxia = 55 ± 11 sec; chronic hypoxia = 61 ± 12 sec, P < 0.05 vs. normoxia). Conclusions: The observation that FMD remains depressed throughout the course of acclimatisation in lowlanders agrees with our findings in highlanders. Thus, it would seem that the reduction in FMD in response to hypoxia does not represent a functional impairment but may well reflect, for reasons that remain to be established, a normal adaptive physiological as opposed to a maladaptive pathological response.