INTRODUCTION: The development and deployment of a web-based, self-triage tool for severe respiratory syndrome coronavirus 2 (COVID-19 disease) aimed at preventing surges in healthcare utilization could provide easily understandable health guidance with the goal of mitigating unnecessary emergency department (ED) and healthcare visits. We describe the iterative development and usability testing of such a tool. We hypothesized that adult users could understand and recall the recommendations provided by a COVID-19 web-based, self-triage tool. METHODS: We convened a multidisciplinary panel of medical experts at two academic medical schools in an iterative redesign process of a previously validated web-based, epidemic screening tool for the current COVID-19 pandemic. We then conducted a cross-sectional usability study over a 24-hour period among faculty, staff, and students at the two participating universities. Participants were randomly assigned a pre-written health script to enter into the self-triage website for testing. The primary outcome was immediate recall of website recommendations. Secondary outcomes included usability measures. We stratified outcomes by demographic characteristics. RESULTS: A final sample of 877 participants (mean age, 32 years [range, 19-84 years]; 65.3% female) was used in the analysis. We found that 79.4% of the participants accurately recalled the recommendations provided by the website. Almost all participants (96.9%) found the website easy to use and navigate. CONCLUSION: Adult users of a COVID-19 self-triage website, recruited from an academic setting, were able to successfully recall self-care instructions from the website and found it user-friendly. This website appears to be a feasible way to provide evidence-based health guidance to adult patients during a pandemic. Website guidance could be used to reduce unnecessary ED and healthcare visits.