Triple-lumen catheters (TLC) are now routinely used in critically ill and multiply injured patients who require multi-port central venous access. An apparent rise in catheter contamination and catheter-related sepsis (CRS) occurred in patients receiving total parenteral nutrition (TPN) through a TLC as opposed to a single-lumen catheter (SLC). A prospective study was performed to determine rates of catheter contamination and CRS in multiple trauma and general surgical-medical patients who received TPN through TLC's and SLC's. Three hundred seven TLC's and 68 SLC's were placed in 234 patients during a 12-month period. There was no statistically significant difference in the rate of contamination or CRS between the two groups although there was a trend toward increased CRS and contamination in the TLC group. TLC's may be used for short-term administration of TPN without significant increase in catheter contamination or CRS.