The aims of our prospective 3-year investigation were (1) to clarify whether high C-reactive protein (CRP) levels are an intermittent or a continuous phenomenon in individual hemodialysis patients and (2) to evaluate a possible relationship between ultrapure dialysis fluid associated CRP levels and an increased prevalence of atherosclerosis in a group of 60 hemodialysis patients treated either with conventional (n = 38) or on-line-produced ultrapure dialysis fluid (n = 22). Primary end points of the study were angiographically confirmed cerebrovascular, cardiovascular, or peripheral vascular events. Measurements of the CRP levels were done every 3 months using a highly sensitive assay. The CRP levels were normal (<0.5 mg/dl) in 45 patients and raised in 15 patients at the time of recruitment. In 87% of the patients with normal CRP levels, ultrapure dialysis fluid was used. The CRP levels measured at recruitment and at various time points thereafter did not differ significantly within patient groups. However, patients with increased CRP concentrations experienced significantly more vascular events as compared with patients with normal CRP levels (11 events vs. 1 event; p < 0.001). The data indicate that continuous induction of acute-phase proteins represents a nontraditional vascular risk factor contributing to the development and progression of atherosclerosis in dialysis patients. Ultrapure dialysis fluid lowers cardiovascular morbidity by preventing/reducing chronic microinflammation.