Introduction: Tubercular pleural effusion is the second most common extrapulmonary form of tuberculosis in India. Developing nations like India face several health challenges and with limited resources, appropriate planning and channelization of the same is the need of the hour. Material and methods: The objective of the study was to determine the role of cartridge-based nucleic acid amplification test (CBNAAT) in the diagnosis of tubercular pleural effusion (TPE) and also to study if any association exists between CBNAAT and pleural fluid adenosine deaminase (ADA) and lymphocyte counts. Clinically suspected TPE, lymphocyte predominant (≥ 70%) exudates (according to the Lights criteria) with ADA ≥ 40 U/L and microbiologically confirmed pulmonary tuberculosis patients with aco-existent pleural effusion were included. Pleural fluid CBNAAT was performed on all the samples. Results: Out of atotal of 75 patients, 57 were males and 18 were females. Alymphocyte predominance of ≥ 70% was seen in 73 subjects (97%). Mean ADA was 61.7 U/L ± 16.2 (SD). Pleural fluid CBNAAT was positive for Mycobacterium tuberculosis (MTB) in 24 patients (32%). Out of these patients, rifampicin resistance was detected in 2 individuals (8.3%). Sputum smear for acid fast bacilli (AFB) was positive in 3 (4%) patients, whereas in sputum CBNAAT MTB was detected in 8 (10.6%) persons. Association between pleural fluid ADA, lymphocyte count and CBNAAT positivity was evaluated by Student T-test. There was asignificant association between higher ADA levels and CBNAAT (p value = 0.001). Conclusions: Pleural fluid CBNAAT, owing to its low sensitivity, should not be included in the diagnostic protocol of TPE in high prevalence areas. Ahigh ADA ≥ 40 U/L in combination with Light’s criteria to define exudates, with lymphocyte predominance is sufficient evidence to diagnose TPE and initiate anti-tubercular therapy, thereby deferring the need to perform an invasive pleural biopsy.