To assess the cost-effectiveness of lanthanum carbonate (LC) as a second-line therapy for hyperphosphatemia in end-stage renal disease (ESRD) patients not achieving target phosphorus levels. A cohort of ESRD patients not adequately maintained on calcium carbonate (CC) and three subgroups of patients with baseline phosphorus levels of 5.6 to 6.5 mg/dl, 6.6 to 7.8 mg/dl, and more than 7.9 mg/dl were modeled. The following policy options were considered: continued CC (Policy 1); LC trial-if successful continue LC, if unsuccessful switch to CC (Policy 2). The survival benefit of using second-line LC to improve phosphorus control has been extrapolated from the relationship between hyperphosphatemia and mortality. Lifetime UK National Health Service drug and monitoring costs, expected survival, and quality-adjusted life-years (QALYs) were examined (discounting at 3.5% per annum). Policy 2 had a cost-effectiveness ratio (cost/QALY) of pound25,033 relative to Policy 1. The results show it is particularly cost-effective to treat patients with phosphorus levels above 6.6 mg/dl. The outcomes did not vary significantly during the one-way sensitivity analysis carried out on important model parameters and assumptions except when the utility value for ESRD was decreased by more than 30%. Applying a cost-effectiveness threshold of pound30,000 per QALY, the model shows it is cost-effective to follow current treatment guidelines and treat all patients who are not adequately maintained on CC (serum phosphorus above 5.6 mg/dl) with second-line LC. This is particularly the case for patients with serum phosphorus above 6.6 mg/dl. Our estimates are probably conservative as the possible compliance difference in favor of LC and the reduced number of hypercalcemic events with LC relative to CC was not considered.