SettingStudies evaluating Xpert MTB/RIF Ultra assay (Xpert Ultra) for diagnosing tuberculous meningitis (TBM) are scarce and have reported contrasting results in comparison to Xpert MTB/RIF assay (Xpert). ObjectiveTo evaluate the performance of Xpert Ultra in diagnosing TBM and compare it with Xpert and multiplex polymerase chain reaction (MPCR). DesignXpert Ultra was performed on 244 cerebrospinal fluid (CSF) samples: 56 definite TBM, 148 probable TBM and 40 non-TBM controls. 105/244 CSF samples were also subjected to Xpert and MPCR (IS6110, MPB64, protein B). ResultsThe overall sensitivity of Xpert Ultra in diagnosing TBM from 244 CSF samples was 72.05% (96.42% - definite TBM, 62.83% - probable TBM) with a specificity of 100%. 18 (12.24%) cases [8 definite TBM, 10 probable TBM] were reported rifampicin resistant (RifR) by Xpert Ultra and confirmed by rpoB sequencing. 60 (40.81%) cases [9 definite TBM, 51 probable TBM] were reported rifampicin indeterminate (RifI) by Xpert Ultra (all trace category), out of which 45 [8 definite, 37 probable) were rifampicin susceptible (RifS) and 5 probable cases were RifR on rpoB sequencing. Out of 105 CSF samples subjected to all three techniques, TBM was diagnosed in 70.66%, 28% and 88% by Xpert Ultra, Xpert and MPCR, respectively. ConclusionXpert Ultra detected TBM with higher sensitivity than Xpert. Among trace category, constituting 40% of TBM cases, rpoB gene sequencing confirmed 5 RifR cases.