Background Data on the real-world effectiveness of Remdesivir (RDV) has yielded conflicting results. US Food and Drug Administration granted full approval for RDV on 10/22/20. On 11/20/20, the World Health Organization issued a conditional recommendation against its routine administration in hospitalized patients, regardless of disease severity. We aimed to examine the association between COVID-19 therapeutics and survival among the recipients. Methods Hurley Medical Center, is a 443-bed teaching hospital in Flint, MI. We retrospectively collected basic demographics, treatment data, and outcomes on adults (≥ 18 years of age) with confirmed SARS-CoV-2 infection, hospitalized at our facility from 03/2020 through 02/2022. Mortality predictors were identified using logistic regression. Results During the study period, overall crude 90-day mortality rate was 16% (269/1668). Supplemental oxygen was required by 1,213 patients and 378 needed ventilatory support. Early in the pandemic, 159/1668 patients received Hydroxychloroquine (HCQ). Based on institutional protocol, 51% (858/1668) of the patient received RDV (Figure 1, 2). After adjusting for age, gender, race and Body Mass Index, HCQ was associated with increased risk of mortality (Odds ratio (OR) 1.72, 95% Confidence Interval (CI) 1.14 – 2.59, p-value 0.010). Mortality in the RDV group was also noted to be higher (162/269) (adjusted OR for mortality 1.37, 95% CI 1.03 – 1.83, p-value 0.032). Supplemental oxygen use was associated with mortality regardless of RDV use (adjusted OR 3.39, 95% CI 2.15 – 5.36, p-value < 0.001). RDV showed no mortality benefit in the group requiring mechanical ventilation (MV) (adjusted OR 0.77, 95% CI 0.55 – 1.09, p-value 0.152) (adjusted OR for mortality with MV 18.62, 95% CI 13.02 – 26.63, p-value < 0.001). Figure 1:Institutional protocolFigure 2:Institutional protocol Conclusion This study adds to the growing evidence that more efficacious treatments against COVID-19 respiratory failure are needed once a patient is hospitalized and that antiviral therapies at this late stage may not have the desired effect. This study has several limitations including its retrospective nature and that the RDV group was likely sicker with higher disease severity. We also did not assess the effect of combination therapy such as RDV and steroids on mortality. A need for further studies remains. Disclosures All Authors: No reported disclosures.