•Four nucleic acid amplification tests for SARS-CoV-2 RNA demonstrated comparable performance using clinical specimens.•A limited number of discrepancies were observed in specimens with low viral loads.•The isothermal amplification assay was slightly less sensitive but was one hour faster than the other methods.•Assay selection requires consideration of test performance, instrument/reagent availability, turnaround and throughput. Numerous nucleic acid amplification tests, including real-time, reverse transcription PCR (rRT-PCR) and isothermal amplification methods, have been developed to detect SARS-CoV-2 RNA, including many that have received emergency use authorization (EUA). There is a need to assess their test performance relative to one another. The aim of this study was to compare the test performance of a high complexity laboratory-developed rRT-PCR EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene with other tests: the Atila isothermal amplification assay targeting the nucleocapsid (N) gene and open reading frame 1ab (ORF1ab), the Altona E and spike (S) multiplex, real-time RT-PCR, and the US Centers for Disease Control and Prevention (CDC) N1 and N2 rRT-PCRs. A diagnostic comparison study was performed by testing nasopharyngeal samples from persons under investigation for coronavirus disease 2019 (COVID-19). Assay performance was assessed by percent agreement and Cohen’s kappa coefficient. Positive percent agreement with the SHC EUA reference assay was 82.8 % (95 % confidence interval (CI) 65.0 to 92.9) for Atila, 86.7 % (95 % CI 69.7 to 95.3) for the Altona E and S targets, and 86.7 % (95 % CI 69.7 to 95.3) and 90.0 % (95 % CI 73.6 to 97.3), for the CDC N1 and N2 targets, respectively. All assays demonstrated 100 % negative percent agreement. Kappa coefficients ranged from 0.86 to 0.92, indicating excellent agreement. Performance was comparable among the SARS-CoV-2 nucleic acid amplification methods tested, with a limited number of discrepancies observed in specimens with low viral loads.