Biopsying lung tumours with endobronchial access in patients with respiratory impairment is challenging. However, fine needle aspiration with the endobronchial ultrasound-endoscope via the oesophagus (EUS-B-FNA) makes it possible to obtain tissue samples without entering the airways. Safety of EUS-B-FNA in these patients has not earlier been investigated prospectively. Therefore, this study aimed at assessing feasibility and safety of EUS-B-FNA from centrally located tumours suspected of thoracic malignancy in patients with respiratory insufficiency. The study is a prospective observational study. Patients with indication of EUS-B-FNA of centrally located tumours and respiratory impairment defined as modified Medical Research Council (mMRC) dyspnoea scale score of ≥3, saturation ≤90% or need of continuous oxygen supply were included prospectively in three centres. Any adverse events (AEs) were recorded during procedure and 1-hour recovery. AEs were defined as hypoxemia (saturation <90% or need for increased oxygen supply) or any kind of events needing intervention. Late procedure-related events were recorded during 30-day follow-up. Between April 1, 2020 and January 30, 2021, 16 patients were included. No severe AEs (SAEs) occurred, but AEs were seen in 50% (n=8) and 13% (n=2) of the patients during procedure and recovery respectively. AEs included hypoxemia corrected with increased oxygen supply and in two cases reversal of sedation. Late procedure-related events were seen in 13% (n=2) and included prolonged need of oxygen and one infection treated with oral antibiotics. In this cohort, EUS-B-FNA of centrally located tumours was safe and feasible in patients with respiratory impairment, when examined in the bronchoscopy suite. A variety of mostly mild and manageable complications may occur, a few even up to 30 days post-procedure.