Krishnakumariamma K, Ellappan K, Muthuraj M, et al. - The most severe form of Mycobacterium tuberculosis (Mtb) infection in humans is tuberculous meningitis (TBM), which is also a public health concern worldwide. Researchers here investigated the performance of GeneXpert MTB/RIF (GeneXpert) for the diagnosis of TBM. In addition, Mtb strains isolated from TBM patients were investigated concerning their genetic diversity and drug susceptibility. They collected a total of 293 TBM suspected cerebrospinal fluid (CSF) samples and subjected them to GeneXpert and Mycobacterial Growth Indicator Tube (MGIT 960) culture, respectively. GeneXpert exhibited sensitivity and specificity of 72.7% and 98.5%, respectively by utilizing MGIT 960 as a gold standard (GeneXpert (n = 20, 6.8%) vs MGIT 960 (n = 22, 7.5%)). Overall findings support the utility of GeneXpert for the diagnostic confirmation of TBM; however, they recommend subjecting a GeneXpert negative sample to MGIT 960 culture or LPA to rule out TBM. Among TBM patients in South India, East African Indian lineage was the most predominant and was correlated with drug resistance. They suggest ruling out the discordance between GeneXpert, MGIT 960, and LPA with respect to rifampicin resistance to avert TB treatment failure or relapse.