Objectives: No previous randomized controlled trial (RCT) have been reported examining once every 4 weeks (Q4W) administration of darbepoetin alfa in patients with chronic kidney disease. We report results from a RCT that compared darbepoetin alfa Q4W with continuous erythropoietin receptor activator (C.E.R.A.) Q4W for the correction of anemia and total cost of erythropoiesis-stimulating agents (ESAs) in patients with CKD not on dialysis nor receiving treatment with ESAs in Korea. Methods: Forty-four patients were randomized (1:1) to receive either darbepoetin alfa Q4W or C.E.R.A. Q4W during a 12-week correction period and a 24-week evaluation period. Dosage was adjusted to maintain hemoglobin (Hb) between 10 and 11 g/dL. Two primary end points were assessed: changes in Hb concentration over time during evaluation period and total cost of erythropoiesis-stimulating agents by subject during study period. Results: Patient baseline characteristics and risk factors were well balanced across both treatment groups. Changes in Hb concentration over time during evaluation period were not different between two groups (p = 0.577). Total cost of ESAs by subject during study period were lower in darbepoetin alfa group than C.E.R.A. group (₩ 257,108 ± 118,586 vs ₩ 728,383 ± 409,987, respectively, p < 0.001). The Hb response rate and mean Hb changes from baseline were not different between darbepoetin alfa and C.E.R.A group (100.0 vs 90.0%, p = 0.487 and 1.24 ± 0.82 vs 1.13 ± 1.09 g/dL, p = 0.748, respectively). Adverse event rates were comparable between the treatment groups. Conclusions: Darbepoetin alfa Q4W was comparable in the correction of anemia and superior in terms of cost effectiveness compared with C.E.R.A. Q4W in Korea.