Central line associated blood stream infections (CLABIs) are associated with an increase in length of stay, morbidity, hospital costs, and mortality. In 2009, CLABIs were on the increase at Covenant Healthcare's 55 bed Level III neonatal intensive care unit (NICU). Prior to this practice initiative, there were no standardized central line management practices in the NICU. We retrospectively reviewed the incidence CLABIs for the six months prior to the initiation of the standardization of central line management and then 3 months following the implementation of the new practice policy. Specific outcomes measured were the number of CLABIs, length of stay related to CLABIs, and adherence to the policies and procedures. The project was implemented in four phases: 1) hand hygiene, 2) “scrub the hub”, 3) central line tubing changes, 4) central line insertion, removal, and dressing changes. Although there were no statistically significant changes in the outcome measures, there were clinically significant differences between length of stay and risk for central line infection, incidence of CLABIs, and an increase in adherence to the central line practice change policies. The study showed for every week that is added to the patient stay, the patient was 7 times more likely to have a CLABIs. The rate of central line infection was decreased from 15.6 percent per 1000 line days to zero in 2010.