• ■ Objective: To determine whether the phosphate binder calcium carbonate is effective in preventing hyperphosphatemia in dialysis patients when administered between meals as well as with meals. • ■ Design: An open-label, nonrandomized, cross-over study. • ■ Setting: Three hemodialysis centers where staff is experienced in the conduct of clinical trials. • ■ Patients: Clinically stable adult patients on hemodialysis for end-stage renal disease who were successfully undergoing treated for hyperphosphatemia with calcium carbonate. • ■ Interventions: After a 1 to 7 day washout period from prior calcium carbonate treatment and documentation of baseline hyperphosphatemia, patients underwent a 2-week period in which calcium therapy was reinstituted and titrated to the dose that achieved optimal serum calcium and phosphorus levels. The patients then received their optimized dose of calcium carbonate administered first in divided doses with meals for 2 weeks and then between meals for 2 weeks. • ■ Main outcome measures: Comparison of serum calcium and phosphorus concentrations after 2 weeks of calcium carbonate therapy administered with meals or between meals. • ■ Results: Hyperphosphatemia was prevented by both regimens of calcium carbonate, and there were no significant differences in calcium or phosphorus blood levels when calcium carbonate was administered orally with meals or between meals. No difference in the incidence of adverse effects was noted between the two dosage regimens. • ■ Conclusion: The data suggest that the dosing of phosphate binders such as calcium carbonate to prevent hyperphosphatemia can be more flexible than previously perceived.