© 2014 Asian Pacific Society of Respirology. Background and objective Flexi-rigid pleuroscopy is a useful tool in the work-up of pleural effusions, but pleural biopsy using flexible forceps can be difficult in some patients. This study evaluated the feasibility, safety and diagnostic value of using a flexible cryoprobe to obtain parietal pleural biopsies during pleuroscopy. Methods This was a single-centre retrospective study. In patients undergoing diagnostic pleuroscopy, pleural biopsy using flexible forceps, followed by a flexible cryoprobe introduced through the pleuroscope, were performed. A pathologist independently reviewed all biopsies. Any complications, particularly bleeding, were recorded. All patients were followed up for ≥6 months (median 12 months (range 7-26)). Results Twenty-two patients (21 males; median age 72 years; 14 right-sided effusions) were included. All underwent flexible forceps biopsies (FFB) and cryoprobe biopsies (CB) of pleura. FFB and CB established a definitive diagnosis in 20/22 (90%). CB successfully obtained pleural tissue suitable for histopathological analysis in all patients. CB was larger than FFB (median, 25-75 IQR of 10, 7-15.8mm vs 4, 3-8mm), and had better preserved cellular architecture and tissue integrity. Crush artefacts were less common with CB (2/22) compared with FFB (21/22). No significant bleeding was reported. Conclusions CB during flexi-rigid pleuroscopy is feasible, safe and effective. Its routine use during flexi-rigid pleuroscopy requires further evaluation. This study evaluated a novel method to obtain pleural biopsies using a flexible cryoprobe during flexi-rigid pleuroscopy. It showed that cryoprobe pleural biopsy technique was safe and provided good quality diagnostic specimens. Its role as a useful adjunct or alternative to conventional pleural biopsies during flex-rigid pleuroscopy requires further evaluation.