OBJECTIVES: The oral fluoropyrimidine capecitabine is as effective but better tolerated than i.v. 5-FU/LV as first-line treatment in patients with metastatic colorectal cancer. Costs associated with the administration route could vary widely according to national rules and medical practice. We compared costs and outcomes of capecitabine, Mayo Clinic and de Gramont regimens as adjuvant treatment for stage III colon cancer. METHODS: We assessed the cost-effectiveness of the three regimens using the French third-party payer perspective, time horizon and efficacy/safety data (adjusted for indirect comparisons) from two published clinical trials [Twelves et al. N Engl J Med 2005; Andre et al. J Clin Oncol 2003]. Medical resource use and related-cost of chemotherapy and side-effect treatment were estimated from the clinical trials and expert opinion. Only grade 3/4 adverse events were considered when comparing capecitabine to the de Gramont regimen. We applied French standard costs to resources consumed and evaluated cost-effectiveness using relapse-free survival as an efficacy indicator. One-way sensitivity analyses were performed varying the cost estimates for each treatment. RESULTS: Capecitabine-treated patients had a mean life duration increase without treatment failure of 1.3 months vs. Mayo (35 months vs. 33.7 months). De Gramont was considered as effective as Mayo. In the base-case analysis, capecitabine is less costly than the Mayo Clinic (€3961.04 vs. €10985.66) and de Gramont (€3697.05 vs. €7266.06) regimens. Capecitabine appeared to be dominant, more effective and less costly than either of the 5-FU regimens. In the sensitivity analyses, capecitabine remained dominant except for the minimum costs scenario vs. de Gramont. In this case, the cost-effectiveness ratio was estimated at €4511.36 per year without relapse. CONCLUSIONS: As adjuvant treatment for colon cancer, capecitabine decreases medical resources consumed, mainly in hospitals. Its approval in this setting is expected to bring cost savings and better outcomes.