OBJECTIVE: To estimate the cost-effectiveness of adjuvant treatment with exemestane vs tamoxifen for early-stage breast cancer after 2-3 years treatment with tamoxifen, in Spain. METHODS: A Markov state-transition model was performed from the National Health System perspective, and simulates the long-term outcomes over 10 and 20 years. The primary outcome was the incremental cost-effectiveness of exemestane scheme in terms of cost per quality-adjusted life year (QALY) gained. The transition probabilities between health states (disease-free survival with or without complications, local recurrence, contralateral breast cancer, systemic recurrence or dead) were derived from the Intergroup Exemestane Study (IES) trial and from secondary Spanish sources. The costs associated with chemotherapy and complications (bone fractures, vaginal bleeding, venous thromboembolism, myocardial infarction) and unit costs (€ 2005) were obtained from Spanish treatment guidelines and Spanish health costs databases. A literature review was conducted to derive the utility data. RESULTS: The average additional QALY per exemestane-treated patients were 0.200 and 0.557, for 10 and 20 years, respectively, compared with that of tamoxifen alone scheme. The additional cost per QALY gained obtained with exemestane was €70,990 and €39,170, respectively. The sensitivity analyses confirmed the robustness of the base case analysis. CONCLUSIONS: According to this model, adjuvant exemestane therapy after 2-3 years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment, with additional costs per QALY gained.