We performed a randomized controlled trial of an attachable subcutaneous cuff for the prevention of central vascular catheter-related infection among patients receiving intensive care. Catheters were placed percutaneously into new sites with or without a cuff and were dressed with polyantibiotic ointment containing polymyxin, neomycin, and bacitracin. Microbial colonization developed in 34.5% of 29 control and 7.7% of 26 cuffed catheters. Catheter-related bloodstream infection occurred with 13.8% of control vs 0% of cuffed catheters. The cuff was not associated with adverse effects. An unexpectedly large proportion (75%) of catheter infections were due to Candida albicans. This may have been due, in part, to the use of polyantibiotic ointment, as suggested by a pooled analysis of previous trials that demonstrated increased Candida colonization of catheters with the ointment, which is not fungicidal. These data suggest that the cuff can reduce the incidence of catheter-related infection among high-risk patients receiving catheter site care with an antibacterial ointment.