Background: COVID-19 has imposed significant burden on healthcare systems worldwide. The need for simple, rapid, and affordable diagnostic tests to support the existing costly and demanding polymerase chain reaction (PCR) assay is very necessary. Methods: This study evaluated the performance characteristics of three (3) COVID-19 rapid antigen test kits: DG Rapid, SD Rapid and SS Rapid. They were compared with the gold standard real-time reverse transcriptase- PCR (rRT-PCR) for the detection of SARS-CoV-2 nucleocapsid antigen in 75 archived samples. Results: Of the 75 samples tested, 38 (50.7%) were positive and 37 (49.3%) were negative for SARS-CoV-2 RNA by rRT-PCR assay. No false positive was recorded. The DG Rapid kit detected 30 (78.9%) true positives and 8 (21.1%) false negatives. SD Rapid kit detected 28 (73.7%) true positives and 10 (26.3%) false negatives, while the SS Rapid kit detected 19 (50.0%) true positives and 19 (50.0%) false negatives. Specificity of each test kit was 100% (CI 95%), but the sensitivity of the DG Rapid, SD Rapid, and SS Rapid kits was 79%, 74%, and 50% (CI 95%), respectively. Higher sensitivities among samples with Ct values <29.99 were recorded for each kit. Also, the DG Rapid kit demonstrated 79% excellent agreement with rRT-PCR, while the SD Rapid and SS Rapid kits demonstrated good agreement with rRT-PCR with 73% and 50% Cohen’s kappa values, respectively. Conclusion: The study suggests that DG Rapid and SD Rapid kits are reliable alternatives to rRT-PCR for the detection of SARS-CoV-2 infection, especially in resource-limited settings like Ghana.