BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the performance of a rapid antigen test against reverse transcription– polymerase chainreaction (RT-PCR) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in a tertiary care centre in South Kerala. In this study, we compared the performance of a rapid antigen test, coronavirus disease-2019 (COVID-19) Ag Respi-Strip, with that of a real-time PCR assay using PerkinElmer Reagent kit. MATERIALS AND METHODS: A descriptive (diagnostic evaluation) study was conducted at a tertiary care teaching hospital in South Kerala. Samples were taken for RAT and real-time reversetranscriptase–polymerase chain reaction (rRT-PCR) (reference standard) from patients visiting fever clinic in Sree Gokulam Medical College and Research Foundation to calculate the sensitivity, specificity and accuracy of the rapid antigen test. Samples were collected by the following protocols approved by the Institutional Research Committee, Sree Gokulam Medical College and Research Foundation, Trivandrum. Signed informed consent was obtained from all participants. Tests were performed in biosafety level 3 laboratories at the Molecular Laboratory, Department of Microbiology, Sree Gokulam Medical College and Research Foundation, Trivandrum. RESULTS: Of the 241 symptomatic participants, 50 were rRT-PCR positive for SARS-CoV-2. Thirty-nine of these patients also tested positive for SARS-CoV-2 by RAT. The overall sensitivity and specificity were 76% and 99.47%, respectively. We got an accuracy of 94.6%. INTERPRETATION AND CONCLUSIONS: With excellent specificity and moderate sensitivity, a rapid antigen test may be used to rule out COVID-19 in patients. The comparison data obtained in this study indicate that this can be used for rapid screening of patients with high SARS-CoV-2 viral load, but the rate of sensitivity is highly dependent on computed tomography value. This method also enables instrument-free and low-cost point-of-care testing. However, it depends on various factors such as viral loads and clinical status, which could significantly influence the final performance of the antigen test. Hence, negative results from an antigen test may need to be confirmed with a molecular test before treatment.