This study reports a prospective observational study in which an infection prophylaxis protocol based on the National Kidney Foundation's Kidney Disease Outcomes and Quality Initiative (NKF-K/DOQI) guideline 15 describing guidelines for the care of the tunneled dialysis catheter at the time of catheter hook-up for dialysis was used. Catheter-related bacteremia (CRB) incidence data were collected for a 24-month study period and compared to retrospectively collected control data for the immediately preceding 9 months in the same patient population under the same conditions except for the prophylaxis protocol. The incidence of CRB fell from an average level of 6.97 per 1000 catheter-days during the control period to an average of 1.68 during the study period. This change was statistically significant. Although the lowered incidence required 6 months to reach its maximum, the decreased infection rate was sustained. The average incidence during the last 18 months of the study period was 1.28 per 1000 catheter-days. Staff compliance with the protocol did require repetitive education and assessment.