Previous research has found that central line-associated blood stream infections (CLABSIs) increased during the COVID-19 pandemic. This article describes the development, implementation, and evaluation of a quality improvement initiative (QI) at one community health system in Canada to reduce CLABSIs between July 2019 and May 2022. The QI initiative included changes in six areas – organizational oversight and accountability, education and training, standardized central line processes, optimized central line equipment, improving data and reporting, and fostering a culture of safety. Over the study period, CLABSIs were reduced by 51% and the use of both central line insertion checklists and central line capped lumens increased.