Hyperphosphatemia in advanced chronic kidney disease (CKD) necessitates the use of phosphate binders. This in vitro study assessed phosphate binding and Fe release properties of the novel iron-based phosphate binder PA21. Phosphate adsorption and Fe release were assessed under conditions simulating administration of PA21 on an empty stomach and full stomach across a pH range to which PA21 would be exposed during passage through the gastrointestinal (GI) tract. PA21 showed a robust phosphate binding capacity over the entire physiologically relevant pH range. The high binding capacity at low pH indicates that phosphate binding could begin in the stomach. Under the current experimental setting, the maximal bound phosphate to Fe ratio was 0.47 mmol P/mmol Fe. The largest amount of Fe release was observed at the lowest pH without phosphate and was much lower in the presence of phosphate. These results are in line with the formation of iron phosphate at low pH, as indicated by X-ray photoelectron spectroscopy and thermodynamic calculations. Fe release was minimal (≤ 0.35%) across pH 2.5 - 8.5. These studies demonstrate that PA21 has potent phosphate binding capacity and low iron release over a physiologically relevant pH range in the GI tract. These features indicate PA21 could be an effective alternative phosphate binder for CKD patients.