In a coordinated national effort reported by the Agency for Healthcare Research and Quality, the use of 2% chlorhexidine gluconate (CHG) has reduced the central line–associated bloodstream infection (CLABSI) rate by 40%. Conversely, a recent randomized clinical trial determined that chlorhexidine bathing did not reduce the CLABSI rate. The objectives of this study were to conduct meta-analysis and clarify the effectiveness of 2% CHG bathing by nurses on CLABSIs in adult intensive care unit patients and to determine the contributing costs attributable to CLABSIs and 2% CHG bathing. Eligible studies that included the outcome of bloodstream infection rate for central lines were considered. A rigorous systematic review protocol and software tools available from the Joanna Briggs Institute via OvidSP were used. Agency for Healthcare Research and Quality tools assisted with identifiable CHG bathing costs. Four studies were included in the meta-analysis for the outcome of primary bloodstream infections, and 2 studies narratively supported the meta-analysis. A relative risk of 0.46 with 95% confidence interval (0.34-0.63) was determined. This significant effect is seen in an overall z-score of 4.84 (P < .0001). This meta-analysis supports that 2% CHG reduces CLABSIs. The estimated cost increase of 2% CHG-impregnated cloths is $4.10 versus nonmedicated bathing cloths. The cost associated with a single CLABSI is 10 times more than the cost of using 2% CHG-impregnated cloths. Nursing provides significant influence for the prevention of CLABSIs in critical care via evidence-based best practices.