Background Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates, but the impact of viral burden on these outcomes is unknown. Methods We conducted a retrospective cohort study of patients hospitalized with COVID-19 from March 30 to April 30, 2020 at two hospitals in New York City. SARS-CoV-2 viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared patient characteristics and outcomes among patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with risk of intubation and in-hospital mortality. Results We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% with a high viral load (Ct30; n=242; P