Objectives: We tested the hypotheses that respiratory muscle endurance training (RMET) improves endurance cycling performance differently in women and men and more so in hypoxia than in normoxia. Design: A prospective pre-post cross-over study with two testing conditions. Methods: Healthy and active women (seven, 24 ± 4 years, mean ± standard deviation [SD]) and men (seven, 27 ± 5 years) performed incremental cycling to determine maximum oxygen consumption (VO _2peak ) and power output (W _peak ) and on different days two 10-km cycling time trials (TTs) in normoxia and normobaric hypoxia (FiO ₂ , 0.135, ~3,500 m equivalent), in a balanced randomized order. Next they performed supervised RMET in normoxia (4 weeks, 5 days/week, 30 min/day eucapnic hyperpnea at ~60% predicted maximum voluntary ventilation) followed by identical post-tests. During TTs, heart rate, ear oximetry reading, and W _peak were recorded. Results: The VO _2peak and W _peak values were unchanged after RMET. The TT was improved by 7 ± 6% (p < 0.001) in normoxia and 16 ± 6% (p < 0.001) in hypoxia. The difference between normoxic and hypoxic TT was smaller after RMET as compared with that before RMET (14% vs. 21%, respectively, p < 0.001). All effects were greater in women (p < 0.001). The RMET did not change the heart rate or ear oximetry reading during TTs. Conclusion: We found a greater effect of RMET on cycling TT performance in women than in men, an effect more pronounced in hypoxia. These findings are congruent with the contention of a more pronounced performance-limiting role of the respiratory system during endurance exercise in hypoxia compared with normoxia and more so in women whose respiratory system is undersized compared with that of men.