Background: Few studies compare oral to intravenous (IV) iron for managing anemia in patients with chronic kidney disease (CKD) not on dialysis. Methods: We enrolled 96 CKD anemic patients on erythropoietin in a randomized, open-label, multicenter, controlled study. Patients received 29 days of oral FeSO<sub>4</sub> (325 mg t.i.d.) or intravenous (IV) iron sucrose (5 doses of 200 mg weekly). Assessments were made up to 14 days after the last dose. Primary endpoints were changes in hemoglobin and ferritin, and clinical success was evaluated from the percent of patients with combined endpoints of rises in hemoglobin/ferritin, hemoglobin/ferritin/TSAT, and hemoglobin/TSAT. Results: There was no significant difference in hemoglobin values between IV and oral therapy. IV iron patients had greater increases in mean serum ferritin (288 ng/ml, p < 0.0001) compared to oral iron patients (–5.1 ng/ml, p = NS). IV iron patients with baseline ferritin <100 ng/ml had a greater increase in hemoglobin (1.4 g/dl) compared to oral iron patients (0.9 g/dl) (p < 0.05). More IV iron patients (54.2%) attained hemoglobin values >11.0 g/dl compared to oral iron patients (31.3%, p = 0.028), and met hemoglobin/ferritin (62.5%), hemoglobin/TSAT (47.9%), hemoglobin/ferritin/TSAT (43.8%), and ferritin/TSAT criteria (54.2%) than oral iron patients (0, 22.9, 0, and 0%, respectively). There were no serious side effects. Conclusions: These CKD patients had increases in both hemoglobin and ferritin following IV iron therapy, whereas those treated with oral iron had increases in hemoglobin without increases in iron stores. Iron sucrose, given weekly as 200 mg IV push over 5 min is an effective and safe anemia treatment in this population.