Most patients with chronic renal failure have anemia, which can be corrected by recombinant human erythropoietin (rHuEpo) treatment. Increase in arterial pressure (AP) was reported in some studies and was related to higher systemic vascular resistance induced either by the rise of erythrocyte mass or the change in various endogenous vasopressors, including the direct action of rHuEpo itself. We investigated the effect of rHuEpo treatment on hemodynamic variables, including small and large arterial compliance in 20 patients with chronic renal failure who were not receiving dialysis (CCT 29 ± 12 mL/min), with Hb levels of 10.4 ± 0.58 g/dL. They were treated with 2,000 units intravenously followed by 80 to 120 s/c units/kg/body weight, with dosage titration according to Hb level. Noninvasive hemodynamic evaluation was performed before the first rHuEpo treatment, 30 min after the first IV rHuEpo administration and at least 3 months later when target hemoglobin (Hb) and hematocrit (Hct) were reached. No rise in AP occurred after rHuEpo administration either short term or long term. The significant hemodynamic changes were a fall in pulse pressure and a rise in large artery compliance, with no change in small artery compliance after 3 months of rHuEpo treatment when Hb and Hct levels were corrected. These findings show improvement in arterial stiffness when Hb is corrected with rHuEpo treatment.