Determining the etiology of a pleural effusion can present a major problem for the clinician. Diagnostic evaluation of pleural effusions should include relevant history, clinical course, radiographic abnormalities, and take into account the patient’s desire and consent for further invasive investigations. The seventies were dominated by specific pleural effusions, but in the last three decades effusions of malignant etiology have dominated. Despite advances in diagnostics, about 20% of pleural effusions remain etiologically unexplained. Objective: we present data on the diagnostic contribution and complications when using a Ramel‘s needle (Wolf’s set) in investigating the nature of pleural effusions from an etiopathogenetic aspect. Methods: This retrospective study included 284 transparietal closed pleural biopsies performed between January 2011 and December 2020. Local anesthesia with 2% lidocaine was applied to the skin and subcutaneous tissue in all subjects (premedication with 1 mg of atropine or 10 mg of apaurin was sporadically applied); a chest radiograph was taken immediately before and within 4 to 12 hours after the procedure to rule out complications. The diagnostic positivity, accuracy and complication rate of the technique were evaluated. Results: 175 men and 109 women (median age 60 years, range 19–88) underwent transparietal pleural biopsy with a Ramel‘s needle, 96% of pleural effusions were unilateral (53% in the right hemithorax). Pleural tissue was obtained in 98%. The most common histological diagnosis included: malignancy (34.7%), nonspecific inflammation and mesothelial hyperplasia (32.3%), chronic inflammation with fibrosis (23.5%), granulomatous disease (4.3%), normal pleura and striated muscle (5.2%). Microbiological examination was performed in 24 samples (8.4%): Mycobacterium tuberculosis was present in 1 case, Escherichia Coli in one and Candida albicans in another patient. No pathogenic bacteria or fungi were identified in the rest of the examined. The procedure was well tolerated. Complications occurred in 7 (2.4%): pneumothorax in 4 patients (1.4%), vasovagal reaction in 2 cases (0.7%), local hematoma (0.3%). Conclusion: closed (percutaneous, blind) pleural biopsy with a Ramel‘s needle appears to be a simple technique, well tolerated, with a low complication rate and high diagnostic efficiency. Closed pleural biopsy has a relatively high sensitivity in the diagnosis of exudative pleural fluid, especially in tuberculous pleurisy and may provide an alternative technique in clinical practice. It can be applied to any unexplained pleural effusion, in cooperative patients with no coagulation abnormalities, in relation to standard biochemical, microbiological and cytological investigations, especially in hospital units without thoracoscopy. In our series, nonspecific inflammation was the most common histological diagnosis, and repeated biopsies significantly increased the diagnostic contribution.