Background: Bamlanivimab and casirivimab/imdevimab are recombinant neutralizing monoclonal antibodies that decrease viral load in patients with coronavirus disease 2019 (COVID-19) and can decrease hospitalizations. Few data exist comparing these two therapies., Objective: Our aim was to compare the efficacy and safety of bamlanivimab and casirivimab/imdevimab in emergency department (ED) patients with COVID-19 who met criteria for monoclonal antibody therapy., Methods: We performed a single-center, open-label, prospective study in adult ED patients with confirmed COVID-19 and high-risk features for hospitalization. Enrolled patients received bamlanivimab or casirivimab/imdevimab, depending on the day of the week that they arrived. We observed patients for post-infusion-related reactions and contacted them on days 5, 10, and 30. The primary outcome was the number of hospitalizations through day 30. In addition, we compared groups with regard to return visits to the ED, symptom improvement, antibody-induced adverse events, and deaths., Results: Between December 17, 2020 and January 17, 2021, 321 patients completed the study. We found no statistically significant difference in the rate of subsequent hospitalization between groups (bamlanivimab: n = 18 of 201 [8.9%] and casirivimab/imdevimab: n = 13 of 120 [10.8%]; p = 0.57). In addition, we found no statistically significant differences between groups regarding return visits to the ED or symptom improvement. One patient had a possible adverse reaction to the treatment, and 1 patient died. Both of these events occurred in the bamlanivimab group., Conclusions: We found no statistically significant differences in rates of subsequent hospitalization or other outcomes for ED patients with COVID-19 when they received bamlanivimab as opposed to casirivimab/imdevimab. Adverse events were rare in both groups., (Copyright © 2021 Elsevier Inc. All rights reserved.)