Background <p>Diagnosing smear-negative pulmonary tuberculosis (SNPTB) remains a major clinical challenge, particularly in high-burden countries. Bronchoalveolar lavage (BAL) and bronchial biopsy may improve diagnostic accuracy. Adenosine deaminase (ADA) has been widely used as a biomarker in tuberculous effusions; however, its role in BAL fluid remains unclear.</p> Objective <p>To evaluate the diagnostic value of ADA activity in bronchoalveolar lavage fluid, in combination with bronchial biopsy, for the diagnosis of smear-negative pulmonary tuberculosis.</p> Methods <p>This prospective observational study included 37 patients with suspected smear-negative pulmonary tuberculosis recruited from the Chest Diseases Department at Alexandria Main University Hospital. All patients had negative sputum acid-fast bacilli (AFB) smears or were unable to produce sputum but had radiological findings suggestive of tuberculosis. Bronchoscopy was performed to obtain BAL fluid for ADA measurement, AFB smear microscopy, and mycobacterial culture, in addition to bronchial biopsy for histopathological examination.</p> Results <p>The mean BAL ADA level among all patients was 10.77 ± 8.83 IU/L. TB-positive patients showed slightly higher ADA levels (11.80 ± 5.05 IU/L) compared with TB-negative patients (10.14 ± 10.55 IU/L); however, the difference was not statistically significant (<i>p</i> = .074). Bronchoscopy achieved an overall diagnostic yield of 38%. Patients with positive BAL findings were significantly younger, and mucosal wall thickening was more frequently observed in this group.</p> Conclusion <p>BAL ADA levels tend to be higher in patients with smear-negative pulmonary tuberculosis but lack sufficient diagnostic accuracy when used alone. A multimodal diagnostic approach combining bronchoscopy, BAL analysis, histopathology, molecular testing, and clinical assessment improves the diagnostic yield in suspected smear-negative pulmonary tuberculosis.</p>