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Background: Rapid advances in TBCB in recent years have allowed its gradual acceptance as a diagnostic method for DLD, and an alternative to surgical lung biopsy . However, the various guidelines have yet to provide clear recommendations for TBCB. This study investigated the diagnostic value of transbronchial cryobiopsy (TBCB) for identifying diffuse lung disease (DLD) .Methods: The clinical data was reviewed of 34 patients who showed initial signs of diffuse lung lesions, interstitial pneumonia, bronchial asthma, lung cancer/infection, or pulmonary alveolar proteinosis; and underwent TBCB from December 2018 to March 2021. The safety and effectiveness of TBCB in identifying the etiology of DLD was analyzed.Results: Clear pathomorphological diagnoses were obtained for 27 (79.4%) patients, based on clinical characteristics and pathology: pulmonary fibrosis, adenocarcinoma, alveolar proteinosis, extrinsic allergic alveolitis, tuberculous granulomatous inflammation, and interstitial pneumonia. Four (11.8%) patients required multi-disciplinary discussion for diagnostic confirmation (of diffuse lesions, interstitial pneumonia, and lung infection). The etiology of 3 cases remained unknown. The rate of DLD diagnosis via TBCB was 91.2% (31/34). Associated with the TBCB procedure, 9 (26.5%) patients developed pneumothorax (6 mild, 3 moderate), and 29 (85.3%) post-biopsy bleeding (all grade 1, requiring suction and compression, but no other intervention or surgery). The average hospitalization cost and length of stay were 7988 RMB (1233 USD) and 5.48 days, respectively.Conclusion: TBCB is safe, cost-effective, requires a short hospitalization, and the diagnostic confirmation rate for DLD is high.