Access-related bacteremia is an important cause of morbidity in chronic hemodialysis patients. The incidence of bacteremia is higher in patients dialyzing through a tunneled central venous catheter (TCVC) compared with an arteriovenous fistula (AVF). Our aim was to explore if this is explained by patient comorbidity. Two groups of chronic hemodialysis outpatients were compared: all patients who dialyzed through a TCVC at any time during 2003 and were fit enough to subsequently have a functioning AVF or renal transplant even if it was after 2003 (Group 1; n=93); and all patients who dialyzed through a TCVC in 2003 and were not fit enough to have a functioning AVF or renal transplant (Group 2; n=119). Episodes of bacteremia (n=71) were identified and those not related to access were excluded. Patients in Group 1 were younger than Group 2 (57.5 years vs. 64.8 years; P=0.001). The incidences of bacteremia in Groups 1 and 2 were, respectively, 0.31 and 0.44 episodes per 1000 patient days while dialyzing through an AVF (P=0.77), and 2.21 and 2.27 per 1000 days while dialyzing through a TCVC (P=0.91). The 3-year actual survival from January 1, 2003 to January 1, 2006 was significantly higher in Group 1 than in Group 2 (80.6% vs. 26.1%; P<0.0001) confirming the higher comorbidity of the patients in Group 2. Patients dialyzing through a TCVC (compared with an AVF) have a significantly higher risk of access-related bacteremia, irrespective of comorbidity.