BACKGROUND: Although many catheter-related bloodstream infections (CR-BSIs) are preventable, measures to reduce these infections are not uniformly implemented. OBJECTIVE: To update an existing evidenced-based guideline that promotes strategies to prevent CR-BSIs. Data Sources: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles.Studies Included: Laboratory-based studies, controlled clinical trials, prospective interventional trials, and epidemiological investigations. Outcome Measures: Reduction in CR-BSI, catheter colonization, or catheter-related infection. SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters; maximal sterile barrier precautions during central venous catheter insertion; use of a 2% chlorhexidine preparation for skin antisepsis; no routine replacement of central venous catheters for prevention of infection; and use of antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (i.e. education and training, maximal sterile barrier precautions and 2% chlorhexidine for skin antisepsis). CONCLUSION: Successful implementation of these evidence-based interventions can reduce the risk for serious catheter-related infection.