The objective of the study was to determine the effect of switching from an open (glass or semi-rigid plastic) infusion container to a closed, fully collapsible plastic infusion container (Viaflex®) on rate and time to onset of central line associated bloodstream infections (CLABSI). An open-label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in three intensive care units in Brazil. The CLABSI rate using open infusion containers was compared to the rate using a closed infusion container. Probability of acquiring CLABSI was assessed over time and compared between open and closed infusion container periods; three-day intervals were examined. A total of 1125 adult ICU patients were enrolled. CLABSI rate was significantly higher during the open compared with the closed infusion container period (6.5 versus 3.2 CLABSI/1000 CL days; RR=0.49, 95%CI=0.26– 0.95, p=0.031). During the closed infusion container period, the probability of acquiring a CLABSI remained relatively constant along the time of central line use (0.8% Days 2-4 to 0.7% Days 11-13) but increased in the open infusion container period (1.5% Days 2-4 to 2.3% Days 11-13). Combined across all time intervals, the chance of a patient acquiring a CLABSI was significantly lower (55%) in the closed infusion container period (Cox proportional hazard ratio 0.45, p= 0.019). CLABSIs can be reduced with the use of full barrier precautions, education, and performance feedback. Our results show that switching from an open to a closed infusion container may further reduce CLABSI rate as well as delay the onset of CLABSIs. Closed infusion containers significantly reduced CLABSI rate and the probability of acquiring CLABSI.