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OBJECTIVE: We examine the lifetime cost-effectiveness of treatment with fluticasone propionate/salmeterol (500/50 microg) compared with no maintenance treatment in COPD in the US. METHODS: A decision-analytic model was developed to estimate lifetime costs and outcomes associated with fluticasone propionate/salmeterol 500/50 microg treatment, salmeterol 50 microg, and fluticasone propionate 500 microg compared to no maintenance treatment in treating COPD from a third-party US payer perspective. The patient population was similar to that of the TORCH clinical trial. Model structure and inputs were obtained from published literature and clinical trial data. All costs are presented in 2006 US dollars. Outcomes included cost per life year (LY) saved and cost per quality-adjusted life year (QALY) gained. Costs and outcomes were discounted at 3% annually. Univariate and multivariate sensitivity analyses were conducted to assess model robustness. RESULTS: Compared to no maintenance treatment, treatment with fluticasone propionate/salmeterol 500/50mug results in a lifetime incremental cost-effectiveness ratio (ICER) of $33,865/QALY. Treatment with salmeterol 50 microg was found to have an ICER of $20,797/QALY. These results are robust to changes in input parameters. Fluticasone propionate 500 microg was dominated by no treatment, though the results were not robust to changes in parameters. CONCLUSIONS: Treatment of COPD with fluticasone propionate/salmeterol 500/50 microg appears to be cost-effective (<or=$50,000/QALY) compared to no maintenance treatment. Similarly, salmeterol 50 microg may be cost-effective compared to no maintenance treatment. Compared with no maintenance treatment, fluticasone propionate 500 microg was effective in reducing number of exacerbations, but failure to differentiate from no maintenance treatment in mortality resulted in it being dominated in the base case