OBJECTIVES: Gastrointestinal Stromal Tumours (GIST) are rare cancers that generate high expenditures in the Mexican Health System. The purpose of the study was to model the economic and health consequences of second-line treatments (previous imatinib 400mg/day failure) in adult patients with GIST in advanced stages within the Social Security Mexican Institute. METHODS: A cost – effectiveness analysis was developed using a Markov modeling approach. The model simulates costs and effectiveness outcomes in a five-year period. The model aimed to compare sunitinib 50mg/day, imatinib 800mg/day and local best supportive care (BSC) as second-line treatments. Transition probabilities of the Markov model were obtained according to clinical trials previously published in the literature. Effectiveness measures were the number of progression-free-months (PFM) and life-years gained (LYG). The analysis was conducted from the healthcare payer's perspective (only direct medical costs were used). Resource use and costs data was obtained from hospital records at Hospital de Oncología CMN “Siglo XXI” in Mexico City (n=12). Both costs and health outcomes were discounted using a 3% annual rate. Probabilistic sensitivity analysis was performed and acceptability curves were constructed. RESULTS: Second line treatment with imatinib showed the highest expected costs (US$37,197.8±1,368.8) followed by sunitinib (US$16,641.0±368.6) and BSC (US$1,900.7±404.2). On the other hand, the best clinical outcomes were obtained by sunitinib in both PFM and LYG (5.64 months, 1.4 years) followed by imatinib (5.28 months, 1.3 years) and BSC (2.52 months, 1.1 years). Imatinib option resulted dominated by sunitinib and the ICER between sunitinib and BSC was of US$49,134.3 per LYG. Results were robust to Monte Carlo second order sensitivity analysis and acceptability curves showed the same results. CONCLUSION: In Mexico, sunitinib second-line treatment was the most cost – effective alternative compared to imatinib. These results should be taken into account by Mexican decision makers in the management of patients with GIST.