Central line associated blood stream infections (CLABSI) among hematology-oncology patients significantly increase morbidity and mortality and remain a universal challenge. Strategies to decrease risk of CLABSI include adherence to standardized practices for central venous line (CVL) care with sustained long-term compliance on the part of caregivers. In our efforts to reduce CLABSI, a multidisciplinary task force was created to systematically introduce standardized CVL insertion and maintenance care bundles in the hematology-oncology inpatient unit. Data was collected in standardized format according to CDC criteria and compared to historical institutional CLABSI rates. During the first year after implementation of these interventions, our CLABSI rate decreased by 68% and rate reduction has been sustained during following two years. The overall impact (2009-2011) includes 40 CLABSIs prevented, 3 lives saved and institutional health care cost savings in excess of 1 million dollars.