Background <p>Extrapulmonary tuberculosis (EPTB) poses a diagnostic challenge due to its paucibacillary nature and low diagnostic yield of traditional methods. Molecular diagnostic tools like Xpert MTB/RIF, Xpert MTB/RIF Ultra, and Truenat MTB offer promising alternatives for the rapid and higher detection rates for pulmonary TB samples. However, the yield of these newly introduced molecular tests on extra-pulmonary samples requires country-specific evaluation and comparative analysis.</p> Methodology <p>This study evaluated the diagnostic performance of Xpert MTB/RIF, Xpert MTB/RIF Ultra, and Truenat MTB assays in detecting EPTB on 211 clinical specimens collected at a tertiary care centre of central India. The assays’ sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPP) were compared against a composite reference standard.</p> Results <p>Xpert MTB/RIF Ultra exhibited the highest sensitivity (50%) for EPTB detection, outperforming the standard GeneXpert MTB/RIF (29.4%) and Truenat MTB (35.3%), with comparable specificity across all three assays. Among the specimen types, pus samples demonstrated the highest (value) diagnostic yield. These findings highlight the superior diagnostic capabilities of Xpert MTB/RIF Ultra, particularly in paucibacillary cases.</p> Conclusion <p>Xpert Ultra demonstrates superior sensitivity for EPTB detection compared to Xpert MTB/RIF and Truenat MTB, making it a promising tool to enhance diagnostic accuracy in paucibacillary TB. Its adoption as a standard diagnostic method could significantly improve EPTB management. These findings advocate for integrating advanced molecular diagnostics into routine tuberculosis workflows to reduce diagnostic delays and improve patient outcomes.</p> Clinical trail number <p>Not applicable.</p>