Central venous lines (CVLs) are used extensively in intensive care units (ICUs) but can sometimes lead to catheter-related blood stream infections (CRBSIs). This study evaluated a "CVL bundle" to see whether the CRBSI rate would decrease, analyze any changes in the flora of CRBSIs, and project any decrease in health care costs. The CVL bundle was implemented on all patients admitted to the ICU starting January 2008. Data from CRBSI rates from 2006 and 2007 were pooled to compare the intervention. A Poisson analysis generated a relative risk reduction. Determination of costs were made by taking the excess length of stay multiplied by other costs (supplies, medications, cost of replacement of CVL) at our institution. Overall infection rates decreased with an improvement in CRBSIs in all ICUs that participated. Although the proportion of gram-negative organisms did not change significantly, there was a decrease in the proportion of gram-positive infections (P = .05) and an increase in fungal infections (P = .04). The total excess cost per organism was determined by the following: total excess cost = excess length of stay + replacement of CVL + drug administration + antibiotic cost. The weighted excess cost took the total excess cost times a correction factor based on organism frequency. The total excess cost of any given CRBSI is approximately $32,254. Preventing CRBSIs can improve patient care while reducing hospital stays, costs, and possible mortality. CVL bundles are fairly easy to perform with reproducible results. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.