Ferric pyrophosphate citrate (Triferic) is a water-soluble iron salt that is administered via dialysate to maintain iron balance and hemoglobin in hemodialysis patients. This double-blind, randomized, placebo-controlled, single-, ascending-dose study was conducted to evaluate the pharmacokinetics and safety of intravenous ferric pyrophosphate citrate in 48 healthy iron-replete subjects (drug, n = 36; placebo, n = 12). Single doses of 2.5, 5.0, 7.5, or 10 mg of ferric pyrophosphate citrate or placebo were administered over 4 hours, and single doses of 15 or 20 mg of ferric pyrophosphate citrate or placebo were administered over 12 hours via intravenous infusion. Serum total iron (sFetot), transferrin-bound iron (TBI), hepcidin-25, and biomarkers of oxidative stress and inflammation were determined using validated assays. Marked diurnal variation in sFetot was observed in placebo-treated subjects. Concentrations of sFetot and TBI increased rapidly after drug administration, with maximum serum concentrations (Cmax) reached at the end of infusion. Increases in baseline-corrected Cmax and area under the concentration-time curve from 0 to the time of the last quantifiable concentration (AUC0-t) were dose proportional up to 100% transferrin saturation. Iron was rapidly cleared (apparent terminal phase half-life 1.2-2 hours). No significant changes from baseline in serum hepcidin-25 concentration were observed at end of infusion for any dose. Biomarkers of oxidative stress and inflammation were unaffected. Intravenous doses of ferric pyrophosphate citrate were well tolerated. These results demonstrate that intravenous ferric pyrophosphate citrate is rapidly bound to transferrin and cleared from the circulation without increasing serum hepcidin levels or biomarkers of oxidative stress or inflammation.