OBJECTIVES To assess cost effectiveness of Letrozole vs Tamoxifen in five-year adjuvant treatment of hormone receptor-positive, post-menopausal early breast cancer patients in Colombia. METHODS The natural history of the disease and the effects of treatment were modeled as a Markov process. Effectiveness was defined as disease-free survival. Transition probabilities for the disease and adverse effects were obtained from the literature. Costs are the median of actual costs for some health insuring firms and the National Cancer Institute, and are expressed in 2007 Colombian pesos (COP). Sensibility analysis were also carried out for costs, effectiveness, discount and model assumptions. RESULTS Compared to Tamoxifen, Letrozole results in an additional relapse-free period of 0.45 years. Each year obtained in this way costs $58,128,304 (COP), or $79,355,466 (COP) with a discount rate of 3%. The results were not sensitive to relapse cost, adverse events and discount. Drug cost was the main variable that affected cost effectiveness: Letrozole is cost effectiveness for Colombia if its cost is lower than $2081 (COP) per tablet. CONCLUSIONS The use of Letrozole has an additional cost per relapse-free year over the Colombian per capita GDP ($7,521,363 (COP) in 2007). Hence, for postmenopausal, early breast cancer hormone receptor positive women in Colombia, the cost-effective alternative is Tamoxifen as adjunvant therapy for five years.