OBJECTIVES To compare cost and effectiveness between monotherapy with octreotide LAR® vs sequential therapy with lanreotide Autogel® and octreotide LAR® (long term somatostatin analogs) in the treatment of patients with acromegaly,from an institutional perspective, in the Mexican setting. METHODS Cost-effectiveness analysis using a decision tree model that simulates the cost and efficacy of the treatment of acromegaly with long term somatostatin analogs: monotherapy with octreotide LAR® vs. sequential therapy with lanreotide Autogel® and octreotide LAR® or vice versa, for a temporary horizon of 18 months. The effectiveness measure was the percentage of patients achieving a reduction in IGF-1 and growth hormone levels, obtained from clinical trials published in international literature. Only direct medical costs were considered in the analysis. Costs were estimated using prices of 2008 and are expressed in US dollars (exchange rate of 11.14 pesos/ 1 US$). RESULTS Octreotide LAR® monotherapy lead to 30% of patients achieving a reduction of IGF-1 and growth hormone to safe levels, whereas sequential therapy achieved 37.8% patients with hormone reduction to safe levels. The treatment with lanreotide Autogel®/octreotide LAR® showed the best average cost $24,792.3, per acromegalic patient treated, followed by the treatment with octreotide LAR®/ lanreotide Autogel® with a cost of $28,925.8 and finally octreotide LAR® monotherapy with a cost of $29,514.0. According to incremental analysis, the treatment with lanreotide Autogel®/octreotide LAR® is the dominant alternative. Univariate sensitivity and probability analyses results show the same trend as the basic scenario. CONCLUSIONS Lanreotide Autogel®/octreotide LAR® is the best cost-effective acromegaly treatment, from the institutional perspective in the Mexican context.