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Background/Objective: The primary objective was to quantify the role of the number of Centers of Disease Control and Prevention (CDC) risk factors on in-hospital mortality. The secondary objective was to assess the associated hospital length of stay (LOS), intensive care unit (ICU) bed utilization, and ICU LOS with the number of CDC risk factors. Methods: A retrospective cohort study consisting of all hospitalizations with a confirmed COVID-19 diagnosis discharged between March 15, 2020 and April 30, 2020 was conducted. Data was obtained from 276 acute care hospitals across the United States. Cohorts were identified based upon the number of the CDC COVID-19 risk factors. Multivariable regression modeling was performed to assess outcomes and utilization. The odds ratio (OR) and incidence rate ratio (IRR) were reported. Results: Compared with patients with no CDC risk factors, patients with risk factors were significantly more likely to die during the hospitalization: One risk factor (OR 2.08, 95% CI, 1.60–2.70; P < 0.001), two risk factors (OR 2.63, 95% CI, 2.00–3.47; P < 0.001), and three or more risk factors (OR 3.49, 95% CI, 2.53–4.80; P < 0.001). The presence of CDC risk factors was associated with increased ICU utilization, longer ICU LOS, and longer hospital LOS compared to those with no risk factors. Patients with hypertension (OR 0.77, 95% CI, 0.70–0.86; P < 0.001) and those administered statins were less likely to die (OR 0.54, 95% CI, 0.49–0.60; P < 0.001). Conclusions: Quantifying the role of CDC risk factors upon admission may improve risk stratification and identification of patients who may require closer monitoring and more intensive treatment.