OBJECTIVE To review the literature on prevention of intravascular catheter-related infections. METHODS The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles. Primary authors were contacted directly if data were incomplete. METHODS Studies met the following criteria unless otherwise stated: Trials were prospective and randomized; catheters were inserted into new sites, not into old sites over guidewires; catheter cultures were done by using semi-quantitative or quantitative methods; and, for prospective studies, catheter-related bloodstream infection was confirmed by microbial growth from percutaneously drawn blood cultures that matched catheter cultures. METHODS Data on population, methods, preventive strategy, and outcome (measured as catheter-related bloodstream infections) were gathered. The quality of the data was graded by using preestablished criteria. RESULTS The recommended preventive strategies with the strongest supportive evidence are full barrier precautions during central venous catheter insertion; subcutaneous tunneling short-term catheters inserted in the internal jugular or femoral veins when catheters are not used for drawing blood; contamination shields for pulmonary artery catheters; povidone-iodine ointment applied to insertion sites of hemodialysis catheters; specialized nursing teams caring for patients with short-term peripheral venous catheters, especially at institutions with a high incidence of catheter-related infection; no routine replacement of central venous catheters; antiseptic chamberfilled hub or hub-protective antiseptic sponge for central venous catheters; and use of chlorhexidine-silver sulfadiazine-impregnated or minocycline-rifampin-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies that do not incorporate antimicrobial agents (for example, maximal barrier precautions). CONCLUSIONS Simple interventions can reduce the risk for serious catheter-related infection. Adequately powered randomized trials are needed.