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IRON deficiency anemia is one of the essential problems in HEMODIALYSIS patients and with presence of IRON deficiency, EPO does not have any effect on HEMATOCRIT (HCT) level and transferring saturation percentage (TSP). However, injection of IV IRON together with EPO improves responses to anemia treatment. The aim of this study was to determine the effect of IRON (oral or IV) prescription with or without EPO on HCT levels and TSP in HEMODIALYSIS patients in Semnan City. In this case-control study HEMODIALYSIS patients were assessed for three months during one year. At first, demographic data including age, sex, marriage situation and treatment time were collected and recorded. Then, drug prescription was investigated, HCT measurement was controlled monthly and TSP for three months. Investigation of data indicated that in patients who used three components (IRON oral, IV and EPO) or used IRON IV and EPO the levels of HCT and TSP increased significantly (P< 0.05), whereas use of IRON IV or IRON IV and oral indicated a significant increase only in TSI (P< 0.05). Also, the use of only oral IRON did not have a significant effect (P> 0.05). The obtained results showed that oral IRON is unlikely to keep IRON level in response to EPO. Therefore, patients with anemia and IRON deficiency will always require intravenous IRON therapy and it is better that they use three components all together.