Abstract: Objective To observe the impact of the way of maintenance iron supplementation on hemoglobin variability (Hb-Var) in hemodialysis (HD) patients. Methods A total of 160 HD patients in zhongshan hospital affiliated to Xiamen University from January, 2015 to December, 2015 were consecutively enrolled into this study. The patients were randomly allocated into vein group and oral group. Hb-Var were analyzed after iron supplementation through vein (iron sucrose injection 100 mg per week) or oral (iron polysaccharide complex 100 mg per day) during the maintain treatment of renalanemia. All patients were followed up for one year. Results Assessment of Hb-Var:① The residual standard deviation (SD) of the intravenous injection (IV) group was significantly lower than that in oral group[(8.04±4.58)g/L vs. (12.25±6.85)g/L, P=0.042]. ② The hemoglobin (Hb) amplitude of the IV group was lower than that in oral group[(15.88±8.07)g/L vs. (27.00±15.88)g/L, P=0.015]. ③ The individual changes and SD of the IV group which measured continuously in the adjacent time points was lower than that in oral group[respectively (8.64±4.91)g/L vs. (13.69±7.60)g/L and (6.25±3.76)g/L vs. (11.23±8.49)g/L, both P<0.05]. ④ The proportion of each groups such as above, within and below the scope of the targe (Hb:110-130 g/L):IV group was 12.85%, 71.14% and 16.01%, oral group was 6.9%, 55.17% and 37.93% (χ²=7.164, P=0.028). Transferrin saturation (TAST) and serum ferritin (SF) increased in the IV iron group[(29.29±11.80)% vs. (39.36±12.3)%, P=0.025 and (375.39±223.77)ng/ml vs. (463.05±303.26)ng/ml, P=0.005]. Conclusion The supplement methods of iron supplementation can influence Hb-Var. IV iron treatment would be more available in keeping continuous qualified Hb than oral treatment. The reason may be concerned with the stability of iron storage and the raise of ferric ion availability.