Introduction:Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD).Methods:A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD.Results:43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6–82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3–96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8–14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8–8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9–2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively.Conclusions:TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres.