© 2020 by the American Society of Nephrology. Background and objectives Ferric citrate is an oral medication approved for treatment of iron deficiency anemia in patients with CKD not requiring dialysis. The relative efficacy of ferric citrate versus ferrous sulfate in treating iron deficiency in patients with CKD is unclear. Design, setting, participants, & measurements We randomized 60 adults with moderate to severe CKD (eGFR 15–45 ml/min per 1.73 m2) and iron deficiency (transferrin saturation [TSAT] ≤30% and ferritin ≤300 ng/ml) to ferric citrate (2 g three times a day with meals, n=30) or ferrous sulfate (325 mg three times a day, n=30) for 12 weeks. Primary outcomes were change in TSAT and ferritin from baseline to 12 weeks. Secondary outcomes were change in hemoglobin, fibroblast growth factor 23 (FGF23), and hepcidin. Results Baseline characteristics were well balanced between study arms. There was a greater increase in TSAT (between-group difference in mean change, 8%; 95% confidence interval [95% CI], 1 to 15; P=0.02) and ferritin (between-group difference in mean change, 37 ng/ml; 95% CI, 10 to 64; P=0.009) from baseline to 12 weeks in participants randomized to ferric citrate as compared with ferrous sulfate. Similarly, as compared with ferrous sulfate, treatment with ferric citrate resulted in a greater increase in hepcidin from baseline to 12 weeks (between-group difference, 69 pg/ml; 95% CI, 8 to 130). There were no between-group differences in mean change for hemoglobin (0.3 g/dl; 95% CI,-0.2 to 0.8), intact FGF23 (-29 pg/ml; 95% CI,-59 to 0.1), or C-terminal FGF23 (61 RU/ml; 95% CI,-181 to 58). The incidence of adverse events did not differ between treatment arms. Conclusions As compared with ferrous sulfate, treatment with ferric citrate for 12 weeks resulted in a greater mean increase in TSAT and ferritin concentrations in individuals with moderate to severe CKD and iron deficiency.