BACKGROUND: Patients with pulmonary vascular disease (PVD) often reveal nocturnal hypoxemia and sleep apnea. We investigated whether exposure to high altitude worsens those conditions. METHODS: In a randomized-controlled crossover trial, stable patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) without resting hypoxemia (PaO2 >
8 kPa at low altitude) underwent respiratory polygraphy at 470 m and during an overnight stay at 2500 m. Patients with severe hypoxemia (SpO2 <
80 % for >
30 min) at 2500 m received supplemental oxygen therapy (SOT) according to safety criteria. Main outcomes were the number of patients who did not require SOT, the effect of high altitude on nocturnal SpO2, oxygen desaturation index (ODI, ΔSpO2 of ≥3 %), apnea-hypopnea index (AHI) and the effect of SOT. RESULTS: Of 27 patients (44 % women, 20/7 PAH/CTEPH, mean ± SD age 62 ± 14 y), 10 (37 %) required SOT during the course of the night (p=0.008 vs. low altitude). At 2500 m vs. 470 m, mean nocturnal SpO2 on ambient air decreased from 91 ± 2 % to 83 ± 4 % (mean change [95 %CI], -8 % [-9 to -6], p <
0.001), time with SpO2 <
90 % increased from 29 ± 27 % to 92 ± 15 % (+63 % [30 to 92], p <
0.001), the ODI increased from 17 ± 14 /h to 42 ± 26 /h (+24.8 /h [12.8 to 36.5], p <
0.001) but AHI remained unchanged. With SOT SpO2 was restored to values at 470 m. CONCLUSIONS: In stable, low-risk patients with PVD, altitude worsened nocturnal hypoxemia but not sleep-disordered breathing. The majority of patients did not require SOT according to predefined safety criteria. When needed, SOT restored low altitude indices of oxygenation. Clinical Trial registration available at www. CLINICALTRIALS: gov NCT05089487.