OBJECTIVES: A long-standing controversy in health-economics is whether future unrelated costs should be included in cost-effectiveness analyses. This discussion is relevant in Chronic Kidney Disease (CKD) for treatments that delay progression towards dialysis and prolong survival. In this study, we determined the influence of future unrelated costs on the cost-effectiveness of the non-calcium based phosphate binder lanthanum carbonate (LC) when used as second-line treatment for hyperphosphatemia in predialysis patients. METHODS: Time-dependent Markov models were constructed; cohorts of 1000 patients were followed lifelong. Patients not reaching target serum phosphate (SP) levels on first-line calcium based phosphate binders (CB) were treated with LC. This strategy was compared with continued CB treatment. Patient-level data were pooled from two clinical trials, one in predialysis and one in dialysis. Reductions in SP levels delayed progression towards dialysis and prolonged survival. RESULTS: For the predialysis cohort, 544 did not achieve target SP levels (<4.6 mg/dl) on CB treatment, and 230 were eligible for LC treatment. Of these, 43 (18.8%) now responded to an 8 week trial of LC. Compared with continued CB treatment, 150 life-years and 101 QALYs were gained with LC. Considerable future unrelated costs were accrued due to prolonged survival while on dialysis. Including these unrelated costs, the cost-effectiveness of second-line LC treatment was £17,150/QALY. Excluding future unrelated costs, net health care cost-savings were estimated due to delayed progression towards dialysis. The net monetary benefit of LC treatment rose from £1302 to £4558 upon exclusion of future unrelated costs. CONCLUSIONS: Second-line treatment of hyperphosphatemia with LC in predialysis CKD patients is cost-effective irrespective of whether future unrelated costs are included. However, this analysis demonstrates the substantial impact of these costs on the cost-effectiveness ratio. We recommend cost-effectiveness guidelines used for reimbursement purposes should specify  exclusion of future unrelated costs in the base case, with inclusion in sensitivity analysis.