Background Before thoracoscopic surgery, diagnosing tuberculous (TB) pleurisy was a medical challenge. Thoracoscopy is the most accurate but expensive method for TB pleurisy diagnosis. TB is common in low-income countries, where financial limitations prevent the use of thoracoscopy, motivating the search for a cheaper alternative. Patients and methods A prospective study was done from January 2019 to January 2023 to evaluate diagnostic methods for patients with exudative pleural effusions (PE) of unknown etiologies. The demographic, radiological, procedural, and histological data of exudative PE patients were analyzed. All patients were examined for adenosine deaminase (ADA) and lymphocyte/neutrophil ratio in pleural fluid. Ultrasound-guided Abrams needle biopsy and video-assisted thoracoscopic surgery pleural biopsies were obtained, and histopathological results were assessed. Results Of 250 patients with PE, 161 (64%) had TB PE, 72 (28.8%) had malignant PE, and 17 (6.8%) had idiopathic PE. Sensitivity of ADA (≥40 U/l) was 88%, lymphocyte/neutrophil ratio (≥0.75) was 86.1%, and their overall sensitivity was 91%. They had 93.2, 86.3, and 100% specificity, respectively. For ultrasound-guided Abrams needle biopsy, the sensitivity of histopathology, culture, and combined histopathology/culture was 66, 46.5, and 78.4%, respectively. All were 100% specific. For thoracoscopic biopsy, the sensitivity of histopathology, culture, and combined histopathology/culture was 100, 86.6, and 100%, respectively. All were 100% specific. The assay sensitivity of pleural fluid and tissue Xpert Mycobacterium tuberculosis/rifampin resistance was 12.5 and 49.7%, respectively. Both were 100% specific. Combining ADA more than or equal to 40 U/l, lymphocyte/neutrophil ratio more than or equal to 0.75, and an ultrasound-guided Abrams needle biopsy yielded 92.4% sensitivity and 100% specificity. Conclusion Combining pleural fluid ADA more than or equal to 40 U/l, lymphocyte/neutrophil ratio more than or equal to 0.75, and ultrasound-guided Abrams needle biopsy can accurately detect TB PE in high-TB populations. It may be an affordable alternative to thoracoscopy in countries with limited resources.