OBJECTIVES: The safety and efficacy of Renagel(r) (sevelamer hydrochloride) in binding phosphate in patients with end stage renal disease and its ability to attenuate the progression of cardiac calcification has been well documented but not the longer-term health and economic consequences. Thus, a model of the predicted long-term consequences of Renagel(r) compared to calcium-based binders (acetate and carbonate) was developed. METHODS: Long-term cardiovascular implications of one year of treatment with phosphate binders in patients on hemodialysis are estimated based on the patient's demographics, co-morbidities, and physiologic and renal parameters. The initial calcification score and expected changes over one year are derived using regression equations developed from the Treat-to-Goal study and translated to cardiovascular disease risk based on equations developed from a long-term cohort study (London). The implications of cardiovascular disease for life expectancy and medical costs are accounted for from a US payer perspective. RESULTS: In a population of 100 patients, the cardio-protective effect of Renagel(r) over 1 year is estimated to prevent 9 future cardiovascular events and to save 18 life years compared with calcium acetate; and 10 events and 18 life years compared to carbonate. These events would cost $205,600 and $226,700 to manage. These benefits are obtained at a net cost of about $37,900 and $19,500, respectively. The incremental cost-effectiveness ratios amount to $2200 and $1100 per (discounted) life year gained; and $4400 and $ 2300 per cardiovascular event prevented. CONCLUSIONS: Widespread use of Renagel(r) for treatment of hyperphosphatemia in patients on hemodialysis may seem like just another burden on already strained health care resources. In the context of dialysis, at a median cost-effectiveness ratio of $46,000 per life year gained, the results of this study provide evidence that such intervention would be economically sound.