Introduction: Tuberculous meningitis (TBM) is a manifestation of extrapulmonary tuberculosis (EPTB) caused byMycobacterium tuberculosis(MTB). The central nervous system is involved in about 1%-2% of all current tuberculosis (TB) cases and about 7%-8% of all EPTB. if not treated early, TBM leads to a high rate of neurological sequelae and mortality.Objective: This study aimed to assess the diagnostic performance of the GeneXpert MTB/rifampicin (RIF) assay in patients with TBM.Methods: A total of 100 suspected TBM cases were enrolled from various departments at tertiary care hospital, Bhopal, Madhya Pradesh, India, and classified as definite, possible, or probable TBM. The clinical samples were tested for microbiological and other cerebrospinal fluid (CSF) testing.Results: Out of 100 cases, 14 (14%) were classified as definite TBM, 15 (15%) were having probable TBM, and 71 (71%) were having possible TBM. Out of a total of 100 participants, all were negative for acid-fast bacilli (AFB) staining. Of the 100 cases, 11 (11%) were positive by mycobacterium growth indicator tube (MGIT) culture, of which only four (36.36%) were positive by GeneXpert MTB/RIF. GeneXpert MTB/RIF detected three (3%) cases that were negative by MGIT culture. Ten (90.9%) of the 11 MGIT-positive culture isolates were found to be RIF sensitive while one (9.1%) was found to be RIF resistant. Three cases tested positive/sensitive by the GeneXpert MTB/RIF but negative by MGIT culture. Six (85%) of the seven GeneXpert MTB/RIF positive cases were RIF sensitive while one (15%) was RIF resistant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 36.36% (95% Confidence Interval (CI) (10.93% to 69.21%)), 96.63% (95% CI (90.46% to 99.30%)), 57.14% (95% CI (25.50% to 83.85%)), 92.47% (95% CI (88.70% to 95.06%)) and 90% (95% CI (82.38% to 95.10%)) for GeneXpert MTB/RIF assay, compared with MGIT culture as the reference standard.Conclusion: Our study found that the sensitivity is lower when compared to culture, so using GeneXpert MTB/RIF alone is not recommended. Overall performance of GeneXpert MTB/RIF assay is noteworthy. The GeneXpert MTB/RIF assay is a potentially accepted test for obtaining an earlier diagnosis, and if it tested positive, the treatment should begin immediately. However, culture must be performed in GeneXpert MTB/RIF negative cases.