Pediatric oncology patients are frequently managed with central lines as outpatients, and these lines confer significant morbidity in this immune-compromised population. We aimed to investigate whether a multidisciplinary, central line maintenance care bundle reduces central line-associated bloodstream infections (CLABSIs) and bacteremias in ambulatory pediatric oncology patients.We conducted an interrupted time-series study of a maintenance bundle concerning all areas of central line care. Each of 3 target groups (clinic staff, homecare agency nurses, and patient families) (1) received training on the bundle and its importance, (2) had their practice audited, and (3) were shown CLABSI rates through graphs, in-service training, and bulletin boards. CLABSI and bacteremia person-time incidence rates were collected for 23 months before and 24 months after beginning the intervention and were compared by using a Poisson regression model.The mean CLABSI rate decreased by 48% from 0.63 CLABSIs per 1000 central line days at baseline to 0.32 CLABSIs per 1000 central line days during the intervention period (P = .005). The mean bacteremia rate decreased by 54% from 1.27 bacteremias per 1000 central line days at baseline to 0.59 bacteremias per 1000 central line days during the intervention period (P < .001).Implementation of a multidisciplinary, central line maintenance care bundle significantly reduced CLABSI and bacteremia person-time incidence rates in ambulatory pediatric oncology patients with central lines. Further research is needed to determine if maintenance care bundles reduce ambulatory CLABSIs and bacteremia in other adult and pediatric populations.