Background: Red blood cell distribution width (RDW) is a quantitative marker of heterogeneity of circulating erythrocytes size and a marker of malnutrition, inflammation and mortality. Erythropoietin resistance index (ERI) is considered as an effective way to check erythropoietin resistance. ERI is related to all-causes of morbidity & mortality in hemodialysis patients. Association with aging and gender have also confirmed progressive increase in RDW with aging and in female gender. Objective: this study aimed to check the relation between RDW & ERI in iron replete hemodialysis patients. Patients and methods: 89 patients matched inclusion criteria followed up for 12 months and data analyzed including age, gender, diabetic status, serum iron, serum ferritin, red blood cell width, Erythropoietin dose per week per kg body weight. Results: Patients included were 36 (40.5%) females and 53(59.5%) males with mean age of 42.7 ± 15.2 years old. Diabetic patients were 51 (57.3%) and non-diabetic were 38 (42.7%). All patients were iron replete as per inclusion criteria with serum ferritin 200-800 ug/dl and transferrin saturation 20-40%. Hemoglobin, RDW & ERI were repeated at 4 checkpoints during the 12-months follow-up period. The average of all (4) readings then processed for Pearson correlation logistic regression to identify the relation between RDW and ERI and we found linear correlation between RDW and ERI. R-square 0.158, P-value < 0.001, this relation was independent of age, gender, hemoglobin level, erythropoietin dose and diabetic status. Conclusion: Our results confirmed the independent relation between RDW and resistance to erythropoietin in iron replete hemodialysis patients.