BackgroundThe associated mortality with COVID-19 has improved compared with the early pandemic period. The effect of hospital COVID-19 patient prevalence on COVID-19 mortality has not been well studied.MethodsWe analysed data for adults with confirmed SARS-CoV-2 infection admitted to 62 hospitals within a multistate health system over 12 months. Mortality was evaluated based on patient demographic and clinical risk factors, COVID-19 hospital prevalence and calendar time period of the admission, using a generalised linear mixed model with site of care as the random effect.Results38 104 patients with COVID-19 were hospitalised, and during their encounters, the prevalence of COVID-19 averaged 16% of the total hospitalised population. Between March–April 2020 and January–February 2021, COVID-19 mortality declined from 19% to 12% (p<0.001). In the adjusted multivariable analysis, mid and high COVID-19 inpatient prevalence were associated with a 25% and 41% increase in the odds (absolute contribution to probability of death of 2%–3%) of COVID-19 mortality compared with patients with COVID-19 in facilities with low prevalence (<10%), respectively (high prevalence >25%: adjusted OR (AOR) 1.41, 95% CI 1.23 to 1.61; mid-prevalence (10%–25%): AOR 1.25, 95% CI 1.13 to 1.38). Mid and high COVID-19 prevalence accounted for 76% of patient encounters.ConclusionsAlthough inpatient mortality for patients with COVID-19 has sharply declined compared with earlier in the pandemic, higher COVID-19 hospital prevalence remained a common risk factor for COVID-19 mortality. Hospital leaders need to reconsider how we provide support to care for patients in times of increased volume and complexity, such as those experienced during COVID-19 surges.