Endothelial injury is prevalent in patients with chronic renal failure (CRF) and may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline, administered over 1 hour, median treatment duration 5 days) on circulating endothelium and/or tissue injury markers such as hepatocyte growth factor, thrombomodulin, von Willebrand factor, and C-reactive protein levels were studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre-dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined absolute and/or functional iron deficiency. The measurements were performed before iron administration and 24 hours after the last infusion. All the markers remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic or other adverse effects were observed. In conclusion, the above high-dose IV iron sucrose supplementation does not cause evident endothelial or other tissue injury in patients with CRF, and is clinically safe.