Background: Establishing a definite diagnosis in cases of pleural effusion is sometimes challenging. Adding ultrasound-guided tru-cut biopsy at the time of obtaining pleural fluid for analysis may increase the diagnostic yield in such cases. Objective: The aim of the current work was to assess the diagnostic yield and the safety of percutaneous ultrasound guided tru-cut needle biopsy in patients with recurrent undiagnosed pleural effusion. Patients and Methods: A retrospective observational study including 45 patients with recurrent undiagnosed pleural effusion who underwent ultrasound-guided tru-cut needle biopsy in the period between January 2019 and October 2020. Results: By using ultrasound-guided needle biopsy, we were able to reach a final histopathological diagnosis in 40 patients with a diagnostic yield of 88.8%. Only 5 cases remained undiagnosed (11.1%). Mesothelioma was found in 13 cases (28.9%) and bronchogenic carcinoma in 7 cases (15.5%). Post-procedural complications included 1 case of pneumothorax (2.2%) and 1 case of hemothorax (2.2%) all resolving with the small caliber chest drain that was inserted at the conclusion of the procedure. Conclusion: It could be concluded that ultrasound-guided needle biopsy is a safe procedure that can be useful in establishing a diagnosis in patients with recurrent pleural effusion. Its high diagnostic yield, while being simpler and cheaper than CT guided biopsy or thoracoscopy, makes it a suitable option in our clinical settings. More studies are needed to validate our findings.