Background and objectives: Catheter-dependent hemodialysis patients may develop access-related and nonaccess- related infections that may be managed in the outpatient arena or in the hospital. The goal of this study was to quantify infections in such patients, to characterize their clinical presentations, and to evaluate factors determining need for hospitalization. Design, setting, participants, & measurements: We collected prospective data on the clinical management of catheter-dependent hemodialysis patients with suspected infection at a large dialysis center. We documented the presenting symptoms, type of infection, pathogen, and whether hospitalization occurred. Results: An infection was suspected in 305 separate cases and confirmed in 88%. The 268 diagnosed infections included catheter-related bacteremia (69%), another access-related infection (19%), and nonaccess-related infection (12%). The overall frequency of infection was 4.62 per 1000 catheter-days. Hospitalization occurred in 37% of all infections, but it varied greatly (72% for nonaccess-related infection, 34% for catheterrelated bacteremia, and 4% for exit-site infection). Among patients with catheter-related bacteremia, the likelihood of hospitalization varied by pathogen, being 53% for Staphylococcus aureus, 30% for Enterococcus, 23% for Staphylococcus epidermidis, and 17% for gram-negative rods (P < 0.001). The likelihood of hospitalization was not associated with age, gender, or diabetes. Fever was a presenting symptom in only 47% of cases of catheter-related bacteremia. Conclusions: Catheter-dependent patients have a high burden of infection. It is important to evaluate patients with suspected infection for various access-related and nonaccess-related infections. A low threshold is indicated for suspecting catheter-related bacteremia because the patients frequently present without fever. © 2011 by the American Society of Nephrology.