Ribeiro Baptista, Bruno, Morgane Faure, Gimbada Benny Mwenge, Capucine Morelot-Panzini, Christian Straus, Thomas Similowski, and Jésus Gonzalez-Bermejo. Feasibility of a hypoxic challenge test under noninvasive ventilation versus oxygen in neuromuscular patients with chronic respiratory insufficiency. High Alt Med Biol. 22:346–350, 2021. Background: The British Thoracic Society recommendations suggest that all patients with an oxygen saturation (SpO2) <85% during a hypoxic challenge test (HCT) should receive supplemental oxygen during air travel. However, neuromuscular patients already using ventilatory support are a specific population and noninvasive ventilation (NIV) during a flight could be an alternative to oxygen for hypoxemia correction, through the augmentation of ventilation. Methods: We conducted a comparative, observational study of neuromuscular patients with chronic respiratory failure, requiring nocturnal mechanical ventilation, who were planning to take a flight. HCT was performed with a ventilated canopy placed over the patient's head or the patient's home ventilator. The positive threshold value chosen for the HCT was <90% SpO2. Results: HCTs were performed on 13 adults with neuromuscular diseases using their home ventilator. Among them, 11 had a positive HCT. For all patients with a positive test, hypoxemia was corrected (SpO2 to >90%) by oxygen therapy (+9 [6–12]%, p = 0.0029). Patient's home ventilator also significantly increased the SpO2 by 8 [7–12]% (p = 0.016). Correction of SpO2 during the HCT was not different between oxygen and NIV. NIV was associated with a significant decrease in pressure, end tidal, carbon dioxide (PetCO2) (−10 [−16 to −7.5] mmHg, p = 0.04). Conclusions: The performance of an adapted HCT in home-ventilated patients with a neuromuscular pathology may be useful in a personalized treatment plan for air travel. NIV can be a new alternative to oxygen therapy for neuromuscular patients planning to take a flight.