Many patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PH) wish to travel to altitude or by airplane, but their risk of hypoxia-related adverse health effects is insufficiently explored.How does hypoxia compared to normoxia affect constant-work-rate-exercise-test (CWRET)-time in PH-patients and which physiological mechanisms are involved?and Methods: Stable PH-patients with resting PaO2 ≥7.3kPa underwent symptom-limited cycle CWRET (60%Wmax) whilst breathing normobaric hypoxic (hypoxia, FiO2:15%) and ambient air (normoxia, FiO2:21%) in a randomized cross-over design. Borg-dyspnea, arterial blood gases, tricuspid regurgitation pressure gradient (TRPG) and mean pulmonary artery pressure/cardiac output ratio (mPAP/CO) by echocardiography were assessed before and end-CWRET.28 patients (13 women), median(quartiles) age 66(54;74)years, mean pulmonary artery pressure 41(29;49)mmHg, and pulmonary vascular resistance 5.4(4;8)WU were included. Under normoxia and hypoxia, CWRET-time were 16.9(8.0;30.0) and 6.7(5.5;27.3) min, median difference (95%CI) -0.7(-3.1 to 0.0) min corresponding to -7(-32 to 0.0)%, p=0.006. At end-exercise in normoxia and hypoxia, median values and differences in corresponding variables were: PaO2 8.0 vs. 6.4, -1.7(-2.7 to -1.1) kPa; arterial oxygen content 19.2 vs. 17.2, -1.7(-3 to -0.1) ml/dl; PaCO2 4.7 vs. 4.3, -0.3(-0.5 to -0.1) kPa; lactate 3.7 vs. 3.7, 0.9(0.1 to 1.6) mmol/l, p<0.05 all differences. Borg-scale 7 vs. 6, 0.5(0 to 1), tricuspid pressure gradient 89 vs. 77 -3(-9 to 16) mmHg and mPAP/CO 4.5 vs. 3.3, 0.3(-0.8 to 1.4) WU remained unchanged. In multivariable regression, baseline PVR was the sole predictor of hypoxia-induced change in CWRET-time.In PH-patients, short-time exposure to hypoxia was well tolerated but reduced CWRET-time compared to normoxia in association with hypoxemia, lactacidemia and hypocapnia. Since pulmonary hemodynamics and dyspnea at end-exercise remained unaltered, the hypoxia-induced exercise limitation may be due to a reduced oxygen delivery causing peripheral tissue hypoxia, augmented lactic acid loading and hyperventilation.