Abstract Background Robust infection control (IC) measures were deployed across healthcare institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment (PPE), enhanced contact precautions, and emphasis on hand hygiene. The impact of these IC measures on the rates of hospital-acquired infections (HAIs), such as multidrug-resistant organisms (MDROs), device-related infections (DRIs), Clostridium difficile infection (CDI), and respiratory viral infections (RVIs) is not known. Here, we aim to evaluate the effect of the enhanced IC practices on the occurrence of various HAIs in a comprehensive cancer center. Methods We analyzed the monthly HAIs rates from September 2017 through March 2022, including data 42 months pre-pandemic (September 2016-February 2020) and 24 months during the pandemic (March 2020-August 2021). Reported HAIs were calculated using denominators of patient days for CDI and MDROs, per 1,000 admissions for RVIs, and catheter days for DRIs. The incidence rate ratios (IRR) were calculated for all HAIs. Results When comparing pre-pandemic to the pandemic period, a significant increase in the overall incidence rate (IR) of MDROs from 0.56 to 0.67 per 1,000 patient days with an IRR of 1.19 (95% CI 1.02-1.39), a decrease in the IR of CLABSIs and a stable IR of CAUTIs and VAEs were observed (Table 1). A significant decrease was observed in the IR of CDI (IRR 0.65 (95% CI 0.55-0.78)). The total IR of hospital-acquired RVIs per 1,000 admissions (5.24 to 1.82; IRR 0.36; 95% CI 0.30-0.44) decreased, as did each respiratory virus (Respiratory Syncytial Virus (0.51 to 0.15; IRR 0.30), Influenza (0.50 to 0.24; IRR 0.50), Parainfluenza (1.21- to 0.34; IRR 0.28), Rhinovirus (1.91 to 0.5; IRR 0.26), and Human Metapneumovirus (0.19 to 0.05; IRR 0.24) during their respective respiratory viral seasons (Figure 1). Table 1.Comparison of hospital-acquired infection incidence rates during pre-pandemic and pandemic periods.Abbreviations. IR, incidence rate; IRR, incidence rate ratio; MDRO, multidrug-resistant organisms; ESBL, extended-spectrum beta-lactamase; PsA, Pseudomonas aeruginosa; CRE, carbapenem-resistant Enterobacterales; LabID, laboratory identified; MRSA, methicillin-resistant Staphylococcus aureus; CDI, Clostridium difficile infection; CAUTI, catheter-associated urinary tract infection; VAE, ventilator-associated events; CLABSI, catheter-associated bloodstream infection; RVI, respiratory viral infections; RSV, respiratory syncytial virus.Figure 1.Nosocomial respiratory viral infections diagnosed at MD Anderson Cancer Center prior to and during the COVID-19 pandemic Conclusion Implementing strict IC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs. However, whether these enhanced measures, such as masking at all times as part of patient care, are needed during the upcoming respiratory viral seasons is not known. Disclosures Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.