Most children receiving cancer treatment require a central venous catheter (CVC), putting them at risk for central line–associated bloodstream infections (CLABSI). As patients are discharged home with a CVC in place, caregivers are expected to maintain the CVC following an in-hospital education session before their first discharge home. Following a review of the literature, the education process was modified to improve the quality of education for caregivers. While the existing step-by-step handbook was reviewed and deemed aligned with best practices, other materials were added for this project: a caregiver skills competency checklist, a handout reviewing oral care and hygiene in the home, and a guide for nurses on what materials to provide families at the time of diagnosis. Additionally, caregivers were required to receive two additional CVC care reinforcement sessions during subsequent admissions to the inpatient units, which involved redemonstrations of skills using the competency checklist. Home-acquired CLABSI in pre- and postintervention groups were compared, and compliance of reinforcement education was measured. Though no statistical significance was found, the odds of experiencing a CLABSI were found to be higher in the preintervention group for mucosal-barrier injury (odds ratio = 2.23; 95% confidence interval [0.43, 22.10]) and laboratory-confirmed bloodstream infections (odds ratio = 4.53; 95% confidence interval [0.59, 203.71]). The clinical significance of reducing home-acquired CLABSI has a positive impact on patient outcomes by decreasing morbidity and mortality, inpatient lengths of stay, and overall health care costs.