Background Most dialysis patients require phosphate binders to control hyperphosphatemia. Ferric citrate has been tested in phase 2 trials as a phosphate binder. This trial was designed as a dose-response and efficacy trial. Study Design Prospective, phase 3, multicenter, open-label, randomized clinical trial. Setting & Participants 151 participants with hyperphosphatemia on maintenance hemodialysis therapy. Intervention Fixed dose of ferric citrate taken orally as a phosphate binder for up to 28 days (1, 6, or 8 g/d in 51, 52, and 48 participants, respectively). Outcomes Primary outcome is dose-response of ferric citrate on serum phosphorus level; secondary outcomes are safety and tolerability. Measurements Serum chemistry tests including phosphorus, safety data. Results 151 participants received at least one dose of ferric citrate. Mean baseline phosphorus levels were 7.3 ± 1.7 (SD) mg/dL in the 1-g/d group, 7.6 ± 1.7 mg/dL in the 6-g/d group, and 7.5 ± 1.6 mg/dL in the 8-g/d group. Phosphorus levels decreased in a dose-dependent manner (mean change at end of treatment, −0.1 ± 1.3 mg/dL in the 1-g/d group, −1.9 ± 1.7 mg/dL in the 6-g/d group, and −2.1 ± 2.0 mg/dL in the 8-g/d group). The mean difference in reduction in phosphorus levels between the 6- and 1-g/d groups was 1.3 mg/dL (95% CI, 0.69 to 1.9; P < 0.001), between the 8- and 1-g/d groups was 1.5 mg/dL (95% CI, 0.86 to 2.1; P < 0.001), and between the 8- and 6-g/d groups was 0.21 mg/dL (95% CI, −0.39 to 0.81; P = 0.5). The most common adverse event was stool discoloration. Limitations Sample size and duration confirm efficacy, but limit our ability to confirm safety. Conclusions Ferric citrate is efficacious as a phosphate binder in a dose-dependent manner. A phase 3 trial is ongoing to confirm safety and efficacy.