Purpose: The purpose of this study was to examine the effect of maximal sterile barrier precaution on the central venous catheter-related infection and subsequent cost savings. Methods: Study subjects were 462 hospitalized patients with central venous, catheter of more than 48 hours duration. Data collection period was from April 2008 to February 2009 at a tertiary university hospital in Seoul. Subjects were randomly assigned to either the treatment or the usual care group. Patients in the treatment group (n=209) were treated by staff using maximal sterile barrier precautions and the comparison group(n=253) received traditional care. Results: Central venous catheter-days was2,821 in treatment group and 3,515 in comparison group. The incidence density of central venous catheter-related infection was 2.1 times higher in the comparison group (8.2 per 1,000 catheter-days) compared with the treatment group (3.9 per 1,000 catheter-days). The incidence density of central venous catheter-related bloodstream infection was 4.54 times higher than in the comparison group (3.2 per 1,000 catheter-days) compared with the treatment group (0.7 per 1,000 catheter-days). The attributable cost of central venous catheter-related infection in the treatment group was 10,174,197 won and that of the comparison group was 22,224,554 won. Attributable cost by area was also significantly lower compared with that of the comparisons. Conclusion: The maximal sterile barrier precaution during central venous catheter insertion was an effective intervention to reduce central venous catheter-related infection rate and provides a significant cost savings.