BACKGROUND: Literature suggests that antibiotic prescribing in COVID-19 patients is high. Currently, there are insufficient data on what drives antibiotic prescribing practices throughout the COVID-19 pandemic. OBJECTIVE: This study sought to determine antibiotic use rates and identify risk factors for antibiotic prescribing in hospitalized patients. It was the first study to assess risk factors for receiving more than 1 course of antibiotics. METHODS: This was a retrospective, multi-center, observational study. Patients admitted from March 1, 2020, to May 31, 2020, and treated for COVID-19 were included. The primary endpoint was the rate of antibiotic use during hospitalization. Secondary endpoints included risk factors associated with antibiotic use, risk factors associated with receiving more than 1 antibiotic course, and rate of microbiologically confirmed infections. RESULTS: A total of 208 encounters (198 patients) were included in the final analysis. Eighty-three percent of patients received at least 1 course of antibiotics, despite low rates of microbiologically confirmed infection (12%). Almost one-third of patients (30%) received more than 1 course of antibiotics. Risk factors identified for both antibiotic prescribing and receiving more than 1 course of antibiotics included increased hospital length of stay (median 12 days), intensive care unit admission, and the necessity for mechanical ventilation. CONCLUSION AND RELEVANCE: There were high rates of antibiotic prescribing with low rates of microbiologically confirmed bacterial co-infection. Many patients received more than 1 course of antibiotics during hospitalization. This study highlights the importance and demand for appropriate antibiotic stewardship practices in COVID-19 patients.