We report a meta-analysis of 4 identical time-series cohort studies of the impact of switching from use of open infusion containers (glass bottle, burette, or semirigid plastic bottle) to closed infusion containers (fully collapsible plastic containers) on central line-associated bloodstream infection (CLABSI) rates and all-cause intensive care unit (ICU) mortality in 15 adult ICUs in Argentina, Brazil, Italy, and Mexico. All ICUs used open infusion containers for 6-12 months, followed by switching to closed containers. Patient characteristics, adherence to infection control practices, CLABSI rates, and ICU mortality during the 2 periods were compared by χ(2) test for each country, and the results were combined using meta-analysis. Similar numbers of patients participated in 2 periods (2,237 and 2,136). Patients in each period had comparable Average Severity of Illness Scores, risk factors for CLABSI, hand hygiene adherence, central line care, and mean duration of central line placement. CLABSI incidence dropped markedly in all 4 countries after switching from an open to a closed infusion container (pooled results, from 10.1 to 3.3 CLABSIs per 1,000 central line-days; relative risk [RR], 0.33 [95% confidence interval {CI}, 0.24-0.46]; P <.001). All-cause ICU mortality also decreased significantly, from 22.0 to 16.9 deaths per 100 patients (RR, 0.77 [95% CI, 0.68-0.87]; P <.001). Switching from an open to a closed infusion container resulted in a striking reduction in the overall CLABSI incidence and all-cause ICU mortality. Data suggest that open infusion containers are associated with a greatly increased risk of infusion-related bloodstream infection and increased ICU mortality that have been unrecognized. Furthermore, data suggest CLABSIs are associated with significant attributable mortality.