Anemia is the most common side effect in patients with chronic kidney disease (CKD) mainly due to lower levels of erythropoietin (EPO) hormone. The aim of the present study is to compare the efficacy of equivalent doses of erythropoiesis stimulating agents (ESAs): short acting (Eprex®; Epoetin alfa) and long acting (Darbepoetin alfa: DA) in the treatment of anemia of CKD adult patients treated from September 2013 to January 2015. A total of fifty five patients were included; 22 patients were treated with Eprex®® (Epoetin alfa) and 33 patients received DA. Different blood indices were assessed in the initial 8 weeks. The equality of the doses was based on the conversion formula (1 μg of DA = 300 IU Eprex®). Treatment with lower dose of DA (0.64±0.07 μg/kg QW) induced a significant increase in hemoglobin (Hb) from week 4 through week 8, while red blood corpuscles (RBCs) and hematocrit (Hct) were significantly elevated in week 8. A significant increase in Hb and Hct were observed starting from week 2 through week 8 parallel with a significant rise in RBCs count, starting from week 3 through week 8 after treatment with DA (0.8±0.06 μg/kg QW), while a significant increment of Hb and Hct were noticed after treatment with DA (1.215±0.11 μg/kg QW) from week 3 to week 7. Administration of higher dose DA (1.37±0.22 μg/kg QW) led to a significant rise of RBCs in week 3, 6 and 7 while Hb and Hct in week 6 and 7. Treatment with equal doses of Eprex® (170.85±16.4 IU/kg and 238±25.9 IU/kg) induced only a mild increase in RBCs in week 7 and 6 respectively, while higher dose of Eprex® (413±40.8 IU/kg) elevated RBCs significantly at week 8 and Hct in week 6 and 8. Administration of DA QW is more effective than Eprex® QTIW in terms of target anemia parameters: RBCs, Hb and Hct during the first 8 weeks of administration.