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Background: Coronavirus disease 2019 (COVID-19) has now spread to most countries and regions of the world. Risk factors associated with multi-drug resistant organism (MDRO) infections in patients with COVID-19 have not been well studied yet. In the present study, we aimed to identify the risk factors associated with the MDRO infections and their impact on in-hospital mortality of COVID-19 patients. Methods: This retrospective cohort study was conducted between December 2019 and April 2020 at two tertiary hospitals in Wuhan, China. Data of cases were collected through electronic medical records system. This study was focused on cases with bacterial culture records. Risk factors and outcomes associated with MDRO infections were analyzed using logistic regression model. Results: Of the 2891 patients, 370 patients have bacterial culture results, and MDROs were isolated in 38 patients. Respiratory tract infections (67.3%) were the most common hospital acquired infections. Variables independently associated with MDRO infections were dyspnea at admission (odds ratio (OR) 4.74; 95% confidence interval (CI) 2.06-10.88; P < 0.001), intensive care unit (ICU) admission (OR 5.02; 95% CI 1.99-12.63; P < 0.01), and invasive mechanical ventilation (OR 5.13; 95% CI 2.15-12.27; P < 0.001), adjusted for age and gender. MDROs infection was also a significant risk factor of death for the patients, adjusted for age, gender, severity of illness, ICU admission and mechanical ventilation (OR 1.12, 95% CI: 0.43-2.96, P = 0.817). Conclusion: In our study, dyspnea at admission, ICU admission and invasive mechanical ventilation were associated with the presence of MDRO infections, and clinicians should be alert in MDRO infections in COVID-19 hospitalized patients. [ABSTRACT FROM AUTHOR]