Background: Existing best practices to monitor and prevent health care–associated infections (HAIs) were ineffective during the COVID-19 pandemic due to increased patient susceptibility toward infections, reduced resources, and increased use of agency nurses. Problem: A review of the US hospitals revealed a 60% increase in central line–associate bloodstream infections (CLABSIs) and a 43% increase in catheter-associated urinary tract infections (CAUTIs) in 2020. A large, academic, level 1 trauma center in Houston, Texas, experienced similar challenges at the start of the COVID-19 pandemic. Approach: An interdisciplinary team of nurses, infection preventionists, and hospital educators combined and adapted existing evidence-based practices in a novel way to create a nursing-led toolkit for quality improvement tracking, improving, and sustaining HAI improvements. Outcomes: CLABSI and CAUTI rates were reduced over time following the introduction of the Nurse-Sensitive Indicator Quality Improvement (NSIQI) Toolkit. The CLABSI standardized infection ratio (SIR) decreased by 19%, and the CAUTI SIR decreased by 19.4%. Conclusions: The novel NSIQI Toolkit is a scalable tool for improving and sustaining CLABSI and CAUTI rates, which may have the potential for other nurse-sensitive quality indicators.