The novel coronavirus disease 2019 (COVID-19) has highlighted vulnerabilities in healthcare systems and has brought the world to a standstill single-handedly. Diagnostic testing for COVID-19 is critical for understanding epidemiology, contact tracing, case management and controlling the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription PCR test, the gold standard test, involves fairly complex steps and takes nearly 24-48 h to generate the results. GeneXpert is a rapid nucleic-acid-detection-based test approved by the Indian Council of Medical Research, which can shorten the turnaround time significantly. The study aimed to compare the performance of GeneXpert against the gold standard real-time reverse transcription PCR for SARS-CoV-2. This retrospective study was conducted at a tertiary care centre from 25 March 2020 to 8 December 2020. The nasopharyngeal/oropharyngeal swabs that were sent to the Viral Research and Diagnostic Laboratory for testing of SARS-CoV-2 by GeneXpert [cartridge-based nucleic acid amplification test (CBNAAT)] were included for the study. A total of 270 samples (220 samples positive and 50 samples negative for SARS-CoV-2 by GeneXpert) were simultaneously tested for real-time reverse transcription PCR. Real-time reverse transcription PCR was considered as gold standard test (reference) for calculating the sensitivity and specificity of the GeneXpert (CBNAAT) test. Out of the total samples tested (=270) for SARS-CoV-2, 220 were positive, and 50 were negative for SARS-CoV-2 by GeneXpert. Among 220 GeneXpert SARS-CoV-2-positive samples, 118 (53.64%) were also positive by real-time reverse transcription PCR, while 102 (46.36%) showed negative results by real-time reverse transcription PCR. However, 50 GeneXpert negative samples showed 100% agreement with real-time reverse transcription PCR, i.e. they were also negative by real-time reverse transcription PCR. The GeneXpert sensitivity and specificity for COVID-19 were seen to be 100% (95% CI: 96.92-100%) and 32.89% (95% CI: 25.50-40.97%), respectively, as compared to the gold standard real-time reverse transcription PCR test. The positive predictive value and negative predictive value of GeneXpert for COVID-19 were found to be 53.64% and 100%, respectively. This study highlights that the GeneXpert test is highly sensitive and found to be useful in emergency and challenging situations for rapidly ruling out negative cases. However, due to its relatively low specificity, positive results should be confirmed with real-time reverse transcription PCR. Therefore, it can serve as a valuable tool for patients requiring urgent care by facilitating early diagnosis and management of COVID-19, ultimately contributing to preventing morbidity and mortality.