We performed a cost-effectiveness analysis to determine the effect of maximal sterile barriers (MSBs) on reducing central venous catheter (CVC)--related infections. Use of MSBs when placing CVCs may reduce the risk of infections but is more cumbersome, time-consuming, and expensive than other techniques.We developed a decision analytic model in which a patient could have a CVC placed with either an MSB or a less stringent technique. We calculated total direct medical costs and the incidences of catheter-related bloodstream infections, catheter colonization, and death.Use of MSBs lowered costs (from 621 dollars to 369 dollars per catheter insertion) and decreased the incidences of catheter-related bloodstream infections (from 5.3% to 2.8%), catheter colonization with local infection (from 5.5% to 2.9%) and death (from 0.8% to 0.4%). MSBs improved patient safety throughout all sensitivity analyses.Use of MSBs during CVC insertion likely lowers medical costs and decreases the incidences of catheter colonization, catheter-related bloodstream infections, and death. Cost savings were found over a wide range of clinical and economic assumptions, suggesting that MSBs should be routinely used when CVCs are inserted.