BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can be detected in respiratory samples by Real-time Reverse Transcriptase (RT)-PCR or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs. METHODS: We developed a 3D-printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab. The performance of 3DP and FLNP swabs were compared in a clinical trial of symptomatic patients at three clinical sites (n=291) using three SARS-CoV-2 EUA tests: a modified version of the CDC Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel and two commercial automated formats, Roche Cobas and NeuMoDx. RESULTS: The cycle threshold (C(t)) values from the gene targets and the RNase P gene control in the CDC assay showed no significant differences between swabs for both gene targets (p=0.152 and p=0.092), with the RNase P target performing significantly better in the 3DP swabs (p & 0.001). The C(t) values showed no significant differences between swabs for both viral gene targets in the Roche cobas assay (p=0.05 and p=0.05) as well as the NeuMoDx assay (p=0.401 and p=0.484). The overall clinical correlation of COVID-19 diagnosis between all methods was 95.88% (Kappa 0.901). CONCLUSIONS: 3DP swabs were equivalent to standard FLNP in three testing platforms for SARS-CoV-2. Given the need for widespread testing, 3DP swabs printed on-site are an alternate to FLNP that can rapidly scale in response to acute needs when supply chain disruptions affect availability of collection kits.