Background: Differentiating tuberculous from non-tuberculous pleural effusions remains a diagnostic challenge. This study evaluated the diagnostic utility of pleural fluid LDH/ADA ratio in this differentiation.Methods: This prospective observational study conducted at a tertiary care center included 150 consecutive patients with exudative pleural effusions. Pleural fluid analysis included LDH, ADA, and other biochemical parameters. The diagnostic performance of LDH/ADA ratio was evaluated using ROC curve analysis.Results: The study population comprised 72 tuberculous, 58 malignant, and 20 other non-tuberculous effusions. The median LDH/ADA ratio was significantly lower in tuberculous effusions [6.2 (4.8-7.6)] compared to malignant [20.2 (16.4-24.8)] and other non-tuberculous effusions [15.9 (12.8-19.6), p<0.001]. At the optimal cut-off value of 16.5, the ratio demonstrated sensitivity 92.4%, specificity 89.8%, positive predictive value 90.6%, and negative predictive value 91.8%. Multivariate analysis identified LDH/ADA ratio <16.5 as the strongest independent predictor of tuberculous effusion (adjusted OR: 8.64, 95% CI: 4.82-15.46, p<0.001). Conclusion: The LDH/ADA ratio represents a reliable, cost-effective tool for differentiating tuberculous from non-tuberculous pleural effusions, with excellent diagnostic performance at a cut-off value of 16.5. This ratio can be particularly valuable in resource-limited settings where advanced diagnostic tools may not be readily available.