Background: The aim of this study was to consider the significance of pleural fluid adenosine deaminase (ADA) activity combined with lymphocyte/neutrophil (L/N) ratio in the diagnosis of tuberculous pleurisy (TBpl) in a region of intermediate prevalence of tuberculosis (TB). Methods: We collected data from 388 patients with exudative pleural effusions. The final diagnoses were compared to the results from our diagnostic method using pleural fluid ADA and L/N ratio. Results: 108 patients had a final diagnosis of TBpl; 102 cases had high levels of ADA (40 IU/L). When we considered ADA 40 IU/L as a diagnostic criterion, the sensitivity was 94.4%, specificity 87.5%, and posttest posttest probability 74.5%. However, when we considered ADA 40 IU/L combined with the L/N ratio 0.75 as a diagnostic criterion, the specificity and post-test probability were rose to 97.5% and 93%, respectively. The other causes of high ADA and L/N ratios were lymphoma and metastatic carcinoma, but mass-like lesions were found on the chest radiographs or CT scans. Conclusion: To evaluate the causes of exudative pleural effusions in a region of intermediate prevalence of tuberculosis, we recommend measuring the pleural fluid ADA and L/N ratio first. If the result is high and malignancies are not suspected, it may be diagnostic of TBpl.