The recent introduction of triple lumen catheters has facilitated the care of seriously ill patients by providing multipurpose central venous access through a single percutaneous 7 French catheter. This prospective study was performed to examine the complications associated with the use of these catheters in patients receiving long-term total parenteral nutrition (TPN). Seventy-five patients undergoing catheterization were randomly separated into two groups: 36 patients underwent placement of a single lumen catheter (SLC), and 39 patients, a triple lumen catheter (TLC). The two groups were comparable with respect to concomitant infections, treatment with antibiotics, and need for intensive care. Patients in the SLC group received TPN for a mean of 9.7 days and in the TLC group, for a mean of 8.5 days (p = 0.427). However, after 5 days of catheterization, there was a marked increase in the number of TLC removed because of skin entry site infections. SLC were more likely to be used for the full duration of TPN administration (p = 0.025). Catheter tips were cultured by semiquantitative techniques. A higher incidence of catheter sepsis was seen with TLC, 12.8% vs 0% with SLC (p = 0.055). TLC used for TPN are associated with higher rates of catheter entry site infections and systemic sepsis. SLC should be used for TPN administration.