Bacteremia is a frequent complication associated with tunneled, cuffed, permanent catheters (PCs). The incidence, spectrum of infecting organisms, and optimal treatment for catheter-associated bacteremia (CAB) have not been clearly established. In this study, 101 chronic hemodialysis (HD) patients with PCs for blood access were prospectively monitored for infection during a 24-month period. Data recorded for each patient included the number of catheter-days, episodes of suspected bacteremia, blood culture results, method of treatment, complications, and outcomes. All patients with CAB were treated with a 21-day course of intravenous antibiotics. The PC was removed if the patient had uncontrolled sepsis or if other vascular access was ready for use. Once the infection was controlled, catheter salvage was attempted, either by exchanging for a new catheter over a guidewire or treating with antibiotics only, leaving the original PC in place. Catheter exchange was the recommended approach in our program, but this was decided in each case by the treating nephrologist. During this study, there were 15,581 catheter-days, with 86 episodes of CAB, or 5.5 episodes/1,000 catheter-days (95% confidence interval, 4.5 to 6.8/1,000 d). Forty-five infections (52.3%) were caused by gram-positive cocci only, including Staphylococcus aureus, coagulase-negative Staphylococcus, and Enterococcus species. Twenty-three infections (26.7%) were caused by gram-negative rods only, including a wide variety of enteric organisms. Eighteen infections (20.9%) were polymicrobial. Thirty-nine of 86 episodes (45.3%) included at least one gram-negative organism. Five PCs were removed because of severe uncontrolled sepsis, and eight PCs were removed because they were no longer required. Of the remaining 73 cases, attempted PC salvage was successful in 11 of 30 patients (36.7%) treated with antibiotics alone versus 35 of 43 patients (81.4%) who underwent PC exchange in addition to antibiotic therapy (P = 0.0005). The only important complication of CAB was endocarditis, occurring in 3 of 86 episodes (3.5%). We conclude that in our HD units, CAB is relatively common and frequently involves gram-negative bacteria. PC salvage is significantly improved when antibiotic treatment is combined with PC exchange over a guidewire.