Background. e aim of this study was thus to evaluate the feasibility and safety of taking biopsy specimens by cryoprobe from the parietal pleura during semirigid pleuroscope. Methods. In a single-center, observational, prospective study, patients with exudative pleural e usion (EPE) were evaluated with a semirigid pleuroscope between January 2015 and July 2017. Each patient underwent pleural biopsy using exible forceps and exible cryoprobe through pleuroscope following diagnostic thoracentesis and closed pleural biopsy (CPB). Results. A total of 92 patients (median age 64 years) were included in the study, most of whom were men (65.2%). Cytological cell block (CCB) and CPB made de nitive diagnoses in 32/92 (34.8%) and 25/92 (27.5%), respectively; exible forceps biopsy (FFB) and cryoprobe biopsy (CB) established de nitive diagnoses in 84/92 (91.3%) and 91/92 (98.9%), respectively. e sample obtained by CB (9.4 ± 4.9 mm) was signi cantly larger than the other two methods: FFB (4.2 ± 2.3 mm) or CPB (1.9 ± 1.0 mm) (P < 0.0001).e immunohistochemical (IHC) staining was more easily performed with CB (98.9%) compared to either FFB (87.0%) or CPB (13.0%).ere were no signi cant complications or procedure-related deaths. Conclusions. Based on these results, CB during semirigid pleuroscope has a high diagnostic yield, di erentiating EPE of unknown etiology with satisfactory e ectiveness and safety.