OBJECTIVES: In Mexico, breast cancer is the most common tumour in women and by 2010 local estimations forecast that more than 200 thousand Mexican women would need attention due to this disease. The purpose of this study was to evaluate the cost – effectiveness of sequential adjuvant therapy vs. monotherapies with aromatase inhibitors (AI) or tamoxifen in postmenopausal women with Early-Stage breast cancer from the Mexican healthcare payer's perspective. METHODS: We used a ten-year Markov analysis model to estimate costs and effectiveness. Effectiveness measure was the % of patients free of recurrence (local or distant). Transition probabilities were obtained from international published literature. Comparators were: tamoxifen 20mg/day (five years); anastrozole 1mg/day (five years); letrozole 2.5 mg/day (five years) and the sequential therapy with tamoxifen 20mg/day (2.5-years) + exemestane 25mg/day (five-years). Resource use estimations were performed employing hospital records in an oncology hospital from the Social Security Mexican Institute-IMSS in Mexico City (n=104). They included emergency, surgery, chemotherapy, outpatient and inpatient services, drugs, oncology procedures, etc. Costs and effectiveness measures were discounted 3% annually. One-way and probabilistic sensitivity analyses were performed and acceptability curves were constructed. RESULTS: Sequential therapy with tamoxifen followed by cross over to exemestane at 2.5-years yielded 84.2% of patients free of recurrence in the ten-years analysis followed of the two other AI monotherapies (81.6%) and tamoxifen monotherapy (79.5%). The latter showed the lower expected costs (US$23,968.3) followed by the sequential therapy (US$29,077.3), anastrozole (US$30,615.2) and letrozole (US$31,478.3). Sequential therapy was the option most cost effective compared to AI monotherapies. Results were robust to Monte Carlo second order sensitivity analysis. Acceptability curves showed the same results with a mean of 83.7% of certainty. CONCLUSION: Sequential therapies should be considered as options more cost-effective compared to monotherapies. These results should be taken into account by Mexican clinicians in the management of these patients.