OBJECTIVE To determine if antiseptic central venous catheters impregnated with silver sulfadiazine and chlorhexidine (antiseptic) reduce bacterial adherence and biofilm formation without producing local or systemic toxicity. METHODS Prospective, randomized, controlled trial. METHODS Experimental laboratory in a university teaching hospital. METHODS Ten outbred New Hampshire pigs. METHODS Nonimpregnated (control) and antiseptic-impregnated catheters were inserted intravascularly into swine for 7 days. After explantation, the catheters were assessed for bacterial adherence and biofilm formation, and the surrounding tissue was assessed for signs of toxicity. Before retrieval, systemic concentrations of antimicrobials were determined. RESULTS Sequential roll plate and centrifuging were used to detect moderately and tightly adherent bacteria on the outer and luminal surfaces of the catheter. The presence of biofilm was detected by scanning electron microscopy. Tissues surrounding the catheters were examined histopathologically; systemic concentrations of chlorhexidine, sulfadiazine, and silver were determined by atomic absorption and high-performance liquid chromatography. As compared with the controls, antiseptic catheters had significantly (p < .01) fewer moderately and tightly adherent bacteria on outer and luminal surfaces, and fewer adherent bacteria when outer surfaces alone were examined (p < .01). Scanning electron microscopy showed bacterial biofilm and adherence on the control catheters but not on the antiseptic catheters. There were no abnormal histopathologic changes associated with the test catheter, and serum concentrations of the antibacterial agents were shown to be within nontoxic ranges. CONCLUSIONS The antiseptic-impregnated catheters prevented bacterial adherence and biofilm formation and produced no local or systemic toxicity.