Biomarkers of inflammation, especially C-reactive protein (CRP), have been consistently shown to predict poor outcomes in chronic hemodialysis (CHD) patients. However, the determinants of CRP and the value of its monitoring in CHD patients have not been well defined. We conducted a retrospective cohort study to evaluate possible determinants of the inflammatory response in CHD patients with a focus on dialysis catheter utilization. Monthly CRP were measured in 128 prevalent CHD patients (mean age 56.6 years [range 19–90], 68% African Americans, 39% diabetics [DM]) over a mean follow-up of 12 months (range 2–26 months). There were a total of 2405 CRP measurements (median 5.7 mg/L; interquartile range [IQR] 2.4–16.6 mg/L). The presence of a dialysis catheter (p<0.002), cardiovascular disease (p=0.01), male gender (p=0.005), higher white blood cell count (p<0.0001), elevated phosphorus (p=0.03), and lower cholesterol (p=0.02) and albumin (p<0.0001) concentrations were independent predictors of elevated CRP in the multivariate analysis. Additionally, CRP levels were significantly associated with the presence of a catheter, when comparing the levels before and after catheter insertion (p=0.002) as well as before and after catheter removal (p=0.009). Our results indicate that the presence of a hemodialysis catheter is an independent determinant of an exaggerated inflammatory response in CHD patients representing a potentially modifiable risk factor.