Background: Transbronchial cryobiopsy (TBCB) is critical procedure in the diagnosis interstitial lung diseases (ILD). The procedure utilizes cryoprobes of different sizes (1.9-mm or 2.4-mm probes). This study aimed to compare the effect of different cryoprobe types on the outcomes of TBCB. Methods: This study was analyzed from an updated single-center prospective cohort study between September 2018 and January 2020 (NCT04047667). TBCB was performed in patients with ILD using 1.9-mm or 2.4-mm cryoprobes. The size and quality of specimens, complications, and histopathological and multidisciplinary discussion (MDD) diagnoses were compared between the cryoprobes. Results: TBCB was performed on 52 and 164 patients with 1.9- and 2.4-mm cryoprobes, respectively. The specimens obtained using the 2.4-mm probe were significantly larger than those obtained with the 1.9-mm probe (surface area: 24.6 vs. 22.0 mm(2), P<0.001). Both percentages of grossly and microscopically qualified specimens acquired with the 2.4-mm probe were significantly higher than those obtained with the 1.9-mm probe (grossly qualified: 80.1% vs. 66.7%, P<0.001; microscopically qualified: 99.4% vs. 90.4%, P=0.003). No significant differences were found in the incidence of pneumothorax (3.7% vs. 0.0%, P=0.360) or the risk of moderate bleeding (9.1% vs. 11.5%, P=0.612) between the two groups. Additionally, no significant differences were observed in the pathological or MDD diagnostic yields. Multivariate analysis indicated that pathological diagnostic yield in patients with microscopically qualified specimens was significantly higher than that with unqualified specimens. Conclusions: Specimens obtained using the 2.4-mm probe were of significantly better size and quality than those obtained using the 1.9-mm probe. No significant differences were observed between the two probes with respect to the safety profile and diagnostic yield.