In this prospective, randomized, controlled, unblinded study, we compared colonization rates of a standard, unimpregnated central venous catheter (CVC) with rates for silver-coated and chlorhexidine-silversulfadiazine (CH-SS)-impregnated CVC. Patient characteristics, CVC insertion site, indwelling time, and colonization detected by semiquantitative and quantitative microbiologic techniques were documented. Two-hundred-seventy-five critically ill patients were included into the study protocol. One-hundred-sixty standard, 160 silver (S)-coated, and 165 externally impregnated CH-SS CVC were inserted. There was a significant difference in CVC colonization rates among study groups (P = 0.029). There was no difference in the colonization rate and the colonization per 1000 catheter days between standard and S-coated (P = 0.564; P = 0.24) or CH-SS-coated CVC (P= 0.795; P = 0.639). When comparing antiseptic CVC with each other, colonization rates were significantly less with CH-SS-impregnated than with S-coated CVC (16.9% versus 7.3%; P = 0.01; 18.2 versus 7.5 of 1000 catheter days; P = 0.003; relative risk, 0.43; 95% confidence interval, 0.21-0.85). Whereas standard and S-coated CVC were first colonized 2 and 3 days after insertion, respectively, CH-SS CVC were first colonized only after 7 days. In conclusion, antiseptic-impregnated CVC could not prevent catheter colonization when compared with standard polyurethane catheters in a critical care setting with infrequent catheter colonization rates and CVC left in place for >10 days.