Local problem: Central line-associated bloodstream infections (CLABSIs) are associated with increased mortality and costs. In the cardiothoracic ICU (CTICU) of an academic medical center, nine CLABSIs occurred in fiscal year (FY) 2018.Purpose: The aim of this project was to reduce the CLABSI rate in the CTICU and sustain the results. Methods: Nurse residents on the CTICU initiated a quality improvement project with a single intervention and expanded it into an ongoing initiative with additional interventions by the unit-based performance improvement committee. Evidence-based interventions were identified and implemented, including education; rounding; auditing; and other unit-specific interventions, which included "Central Line Sunday, " accountability emails, and a blood culture algorithm with a tip sheet.Results: CLABSI incidence was reduced from nine in FY 2018 to one in each of the subsequent FYs (2019 and 2020), which had similar totals of central line days, and two in FY 2021, which had a slightly higher number of central line days. The CTICU was able to achieve zero CLABSIs from August 2019 through November 2020, more than 365 days.Conclusions: Coupled with strong support from nursing leadership, nurses on the unit successfully reduced CLABSIs by adopting novel, evidence-based strategies; ongoing monitoring; and multiple interventions.