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Background: Studies of inpatient coronavirus disease 2019 (COVID-19) mortality risk factors have mainly used data from academic medical centers or large multihospital databases and have not examined populations with large proportions of Hispanic/Latino patients. In a retrospective cohort study of 4881 consecutive adult COVID-19 hospitalizations at a single community hospital in Los Angeles County with a majority Hispanic/Latino population, we evaluated factors associated with mortality., Methods: Data on demographic characteristics, comorbidities, laboratory and clinical results, and COVID-19 therapeutics were abstracted from the electronic medical record. Cox proportional hazards regression modeled statistically significant, independently associated predictors of hospital mortality., Results: Age ≥65 years (hazard ratio [HR] = 2.66; 95% confidence interval [CI] = 1.90-3.72), male sex (HR = 1.31; 95% CI = 1.07-1.60), renal disease (HR = 1.52; 95% CI = 1.18-1.95), cardiovascular disease (HR = 1.45; 95% CI = 1.18-1.78), neurological disease (HR = 1.84; 95% CI = 1.41-2.39), D-dimer ≥500 ng/mL (HR = 2.07; 95% CI = 1.43-3.0), and pulse oxygen level <88% (HR = 1.39; 95% CI = 1.13-1.71) were independently associated with increased mortality. Patient household with (1) multiple COVID-19 cases and (2) Asian, Black, or Hispanic compared with White non-Hispanic race/ethnicity were associated with reduced mortality. In hypoxic COVID-19 inpatients, remdesivir, tocilizumab, and convalescent plasma were associated with reduced mortality, and corticosteroid use was associated with increased mortality., Conclusions: We corroborate several previously identified mortality risk factors and find evidence that the combination of factors associated with mortality differ between populations., Competing Interests: Potential conflicts of interest. All authors: No reported potential conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)