Central venous catheter (CVC) related infections are a major cause of morbidity and mortality. We undertook a clinical follow-up study in order to determine the value of systemic vancomycin usage before catheter insertion against catheter colonization. During the study period 70 patients with central venous catheters were prospectively studied. Patients were selected to one of two groups. All patients using vancomycin, without any other antibiotics, due to previous catheter related bacteraemia, were selected for group A. At the end of the vancomycin therapy a new CVC was inserted to a new site within an hour after the last dose (8 mg/kg). All the patients who had not used any antibiotics before and during catheter insertion were selected for Group B. None of the patients in both groups received any antibiotics for the duration that their catheters were kept in place. The catheters were removed at the end of the 7th day and cultured. In group A and group B colonization was detected with six (24.4%) and with 34 (75.6 %) CVCs, respectively. In group B colonization was detected with a significantly higher rate in comparison with group A with an odds ratio of 17.53 (95% CI: 4.150-7.054). In group A Gram positive cocci was not isolated from the catheter tip in comparison with group B in which the most commonly isolated organisms were Gram-positive cocci (n:21, 58.3%) (p<0.001). These results observed in a relatively homogeneous patient population, suggest that systemic usage of vancomycin before catheter insertion may reduce the incidence of CVC colonization, especially with Gram-positive cocci, and Gram-negative organisms dominate for the colonization.