Background <p>Tuberculosis (TB) is a multisystemic disease caused by Mycobacterium tuberculosis. Extrapulmonary TB can occur as part of a primary or late, generalized infection. Tuberculous pleurisy is the second most common extrapulmonary tuberculosis.</p> Objectives <p>The objective of this study is to assess and compare the diagnostic efficacy of medical thoracoscopic and ultrasound-guided transthoracic pleural biopsies in the diagnosis of tuberculous pleural effusion (TPE).</p> Methods <p>This is a prospective randomized clinical study of 30 patients suspected of having TPE based on clinical, radiological, and laboratory data and referred for diagnosis.</p> <p>All the patients were randomized into two groups. Group A underwent medical thoracoscopy, while Group B underwent ultrasound-guided transthoracic needle biopsies. Biopsy specimens were subjected to histopathological and microbiological analysis. Patients in group B with inconclusive results underwent subsequent medical thoracoscopy.</p> Results <p>After exclusion of non-tuberculous pleural effusion cases, 24 TPE cases were diagnosed. Medical thoracoscopy was able to diagnose 12 out of 13 cases (92.3%) while ultrasound-guided transthoracic needle biopsy, diagnosed 12 out of 14 cases (85.7%). No statistically significant difference was seen between two procedures (<i>P</i> = 1.00).</p> Conclusion <p>No statistically significant difference is detected in the diagnostic yield of medical thoracoscopy and ultrasound-guided transthoracic needle biopsy in diagnosis of TPE. We suggest ultrasound-guided biopsy for patients suspected of having TPE, as it is less invasive and requires rapid bedside intervention.</p>