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Transbronchial lung cryobiopsy (TBCB) is a reliable method for obtaining histopathological findings in interstitial lung diseases. TBCB is traditionally performed during rigid bronchoscopy, positioning an endobronchial balloon blocker to facilitate bleeding management. Therefore, it can be challenging to implement in Centers without access to anesthesiologic support or dedicated beds for endoscopic procedures. We present a series of 11 patients who underwent 12 TBCBs using a flexible bronchoscope and a 5 Fr endobronchial blocker passing through an uncuffed endotracheal tube, under moderate sedation and spontaneous breathing. All procedures were carried out in an endoscopy suite, using fluoroscopy guidance but without requiring anesthesiologic assistance. TBCB was feasible in all cases, and it demonstrated similar or improved diagnostic yield (90.1%) and safety compared to rigid bronchoscopy. In 1 case, it was successfully repeated due to an inconclusive histological definition at the first attempt. The size of the samples was consistent with the literature, as it was the incidence of pneumothorax (16.6%). Four cases of moderate bleeding and 4 cases of severe bleeding were managed without further complications. To our knowledge, this is the first description of a technique allowing to perform TBCB through an artificial airway without need for either rigid bronchoscopy or general anesthesia. We believe this technique could make TBCB faster, cost-effective, and feasible even in resource-limited settings without compromising on safety. However, further studies are needed to validate these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)