BACKGROUND/AIM Dietary phosphate intake and vitamin D receptor activator (VDRA) regulate fibroblast growth factor 23 (FGF23); iron may modulate FGF23 metabolism. We aimed to determine whether oral iron supplementation influences serum FGF23 concentration in hemodialysis (HD) patients, while excluding the effect of dietary phosphate intake. METHODS This prospective study enrolled 27 maintenance HD patients with iron deficiency and hyperphosphatemia treated with sevelamer-HCl. The phosphate binder was changed from sevelamer-HCl to ferric citrate hydrate (FCH) to maintain constant phosphate levels. VDRA, other phosphate binders, and cinacalcet HCl were not changed. Serum intact FGF23, C-terminal FGF23 (C-term FGF23), intact parathyroid hormone (PTH), 1,25(OH)2D and other parameters were monitored for 12 weeks. RESULTS Serum phosphate levels (5.89 ± 1.45 mg/dl at baseline, 5.54 ± 1.35 mg/dl at 12 weeks) and 1,25(OH)2D levels were unchanged. Serum ferritin levels increased from 25.6 ± 24.3 ng/ml at baseline to 55.8 ± 33.5 ng/ml at 12 weeks with FCH administration. Serum intact FGF23 and C-term FGF23 levels significantly decreased at 12 weeks compared with baseline (2,000 (1,300.0-3,471.4) to 1,771.4 (1,142.9-2,342.9) pg/ml, p = 0.01, and 1,608.7 (634.8-2,308.7) to 1,165.2 (626.1-1,547.8) RU/ml, p = 0.007, respectively); serum intact PTH levels significantly increased (96 (65-125) to 173 (114-283) pg/ml, p < 0.001). CONCLUSIONS Oral FCH administration decreased serum intact FGF23 and C-term FGF23 levels and increased intact PTH levels; phosphate and 1,25(OH)2D levels were unchanged. Oral FCH administration to treat iron deficiency is a possible strategy for reducing serum FGF23 levels independent of phosphate and VDRA.