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The increased usage of intravenous iron in hemodialysis patients during recent years has led to increasing concern over the potential development of iron overload. Current methods for detecting iron overload, transferrin saturation, and serum ferritin are neither sensitive nor specific. Labile plasma iron (LPI) represents a component of nontransferrin‐bound iron and may be a more accurate indicator of impending iron overload. We studied whether LPI measured can serve as an early indicator of impending iron overload and mortality in hemodialysis patients. Chronic hemodialysis patients from two medical centers in Israel and Poland who received intravenous iron were included. Baseline clinical and laboratory parameters were recorded. LPI was measured before and 48 hours after a single IV administration. Correlation of positive LPI with laboratory parameters and 2‐year mortality was evaluated. One hundred and one hemodialysis patients were included in the study. LPI became positive post‐administration in 18 (17.8%) patients. Ferritin levels >526 ng/mL and monthly iron doses >250 mg were associated with positive LPI after intravenous iron. At a 2‐year follow‐up, higher mortality was observed in the positive LPI group (61.1% compared to 25.3%, P ≤.05), although this effect was not statistically significant after multivariate adjustment. A substantial number of hemodialysis patients have positive LPI after intravenous iron administration. LPI positively correlates with laboratory parameters that are currently in routine clinical use for detecting iron overload and with higher intravenous iron dose. Further studies should be conducted to establish the clinical implications of LPI monitoring in hemodialysis patients. [ABSTRACT FROM AUTHOR]