IntroductionThe coronavirus 2019 (COVID-19) pandemic has presented various unprecedented challenges to healthcare systems globally, prompting society to adopt new preventative strategies to curb spread of the disease. Those experiencing homelessness have been particularly impacted because of barriers to practicing social distancing, inability to isolate, and poor access to care. Project Roomkey was established in California as a statewide measure to provide non-congregate shelter options for individuals experiencing homelessness to properly quarantine. On goal in this study was to analyze the effectiveness of hotel rooms as a safe disposition alternative to hospital admission for patients experiencing homelessness and who were also positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsThis was a retrospective, observational study that included chart review of patients who were discharged to the hotel from March 2020–December 2021. We recorded demographic information, index visit details, number of emergency department (ED) visits both a month prior to and following the index visit, admission rates, and number of deaths.ResultsDuring this 21-month study period, a total of 2,015 patients who identified as undomiciled were tested for SARS-COV-2 in the ED for various reasons. Of those patients, 83 were discharged from the ED to the hotel. Of the 83 patients, 40 (48.2%) ultimately tested positive for SARS-CoV-2 during their index visit. Two patients returned to the ED within seven days with COVID-19-related symptoms, and 10 patients within 30 days. Two patients required subsequent admission with COVID-19 pneumonia. No deaths were recorded within the 30-day follow-up period.ConclusionThe availability of a hotel served as a safe alternative to hospital admission for patients experiencing homelessness and who were either suspected or confirmed to have COVID-19. It is reasonable to consider similar measures in the management of other transmissible diseases for patients experiencing homelessness who require isolation.