Carr, Jay, Rachel Stone, Courtney Tymko, Kaitlyn Tymko, Geoff B. Coombs, Ryan L. Hoiland, Connor A. Howe, Michael M. Tymko, Philip N. Ainslie, and Alexander Patrician. Global REACH 2018: the effect of an expiratory resistance mask with dead space on sleep and acute mountain sickness during acute exposure to hypobaric hypoxia. High Alt Med Biol. 21:297-302, 2020. We hypothesized that an expiratory resistance and dead space (ER/DS) mask, a version of which was previously shown to partially alleviate sleep-disordered breathing and headache severity during acute normobaric hypoxia (Patrician et al.), would exhibit similar results in conditions of hypobaric hypoxia. In a randomized, single-blinded, sham-controlled, and sex-matched design, 31 healthy lowlanders rapidly (6-8 hours) ascended from sea level to 4300 m (Cerro de Pasco, Peru) and slept with either an ER/DS mask (n = 15) or sham mask (n = 16). Sleep was assessed (via WatchPAT) and questionnaires collected before sleep and upon waking the morning after. There was no difference in apnea-hypopnea index (AHI) between the ER/DS (77 ± 20 events/h) or sham mask (84 ± 27 events/h; p = 0.57). In addition, there was no alleviation of headache scores, improvement in sleep quality, or acute mountain sickness symptom severity. Both the sham and ER/DS masks were poorly tolerated (∼50% subject noncompliance in both groups). These findings highlight the importance and necessity of field-testing and demonstrate that more testing is needed before ER/DS devices, such as these, can be recommended for prophylactic benefits at high altitude.