The safety and efficacy of a second-generation improved antiseptic catheter impregnated with silver sulfadiazine and increased levels of chlorhexidine on its outer surface and chlorhexidine alone on its luminal surfaces was compared in vitro and in vivo to standard antiseptic catheters impregnated with these antimicrobials on their outer surfaces only. In rat and pig intravenous models, the improved antiseptic catheter was significantly more effective in resisting both outer surface and luminal colonization compared with the standard antiseptic or control catheters. There was no evidence of tissue toxicity in any group.