OBJECTIVES: Hyperphosphatemia leads to increased hospitalizations and mortality in End-Stage Renal Disease (ESRD). First-line therapy in Canada consists primarily of calcium carbonate (CC). We determined the incremental cost-effectiveness ratio (ICER) of the non-calcium phosphate binder lanthanum carbonate (LC) as second-line therapy, from a Canadian healthcare perspective. METHODS: A Markov model was developed to determine the cost-effectiveness of second-line LC after therapy failure on CC, compared with continued CC treatment; or alternatively with second-line Sevelamer (SH). Patient-level data (n=380) from a prospective randomized trial were used for LC and CC drug efficacy. For SH efficacy, an indirect comparison of eight clinical trials was used to calculate a dose-relativity between SH and LC of 2.7:1. Costs, quality of life, mortality and hospitalization rates were based on Canadian data. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Modelling 1,000 dialysis patients, 378 (37.8%) did not achieve target serum phosphate (SP) levels (≤1.78 mmol/L) with first-line CC therapy and were eligible for LC. Of these, 168 (44.4%) responded to LC therapy, resulting in 49 life years and 29 Quality-adjusted life years (QALYs) gained. The ICER of second-line LC treatment compared with continued CC treatment was CAN $13,200 ($4,600-$22,800) per QALY gained. Results were robust to plausible variations in model parameters. One-year drug costs per additional responder to second-line LC therapy were $2,600, compared to $4,300 for first-line LC. The model evaluating second-line use of LC vs second-line use of SH estimated that LC had similar efficacy but was 16% less expensive than SH. CONCLUSIONS: Second-line treatment with LC is cost-effective compared to continued therapy with CC; and is less expensive compared to first-line LC. LC had lower costs compared with SH, due to lower dose requirements for similar efficacy. These results reinforce current treatment guidelines to treat patients not achieving target SP levels on CC with second-line LC.