© 2019 by the Oncology Nursing Society. BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are associated with an increased risk of mortality, prolonged hospitalizations, and inflated cost of care. Patients in the hematology-oncology specialty unit are at greater risk of developing CLABSIs because of their immunocompromised state and high number of central line (CL) days. OBJECTIVES: The aim of the EPIC 2 project was to reduce CLABSI rates on a hematology-oncology specialty unit with historically high CLABSI rates despite prior quality improvement efforts. METHODS: EPIC 2 used the theory of planned behavior as the framework for changing patient behavior and was based on evidence from the Partners in Your Care© handwashing study that successfully engaged patients to hold healthcare professionals accountable. FINDINGS: The three-month preintervention average CLABSI rate was 5.69. During the intervention period, the average rate was 3.24. This accounted for a 43% reduction in CLABSIs. Participants in the EPIC 2 project reported feeling empowered to speak up against improper CL care.