OBJECTIVES: This study aimed to model the cost-effectiveness of pre-hospital compared with in-hospital thrombolysis for ST-elevation myocardial infarction (STEMI) from the Brazilian National Health System perspective. METHODS: A decision-analytic model was used to model these two strategies. Study endpoint was life-years gained. Resources use and costs were estimated from the National Health System perspective. Decision tree and Markov Model were constructed using the results from published clinical trials. Costs were applied in Real (R$), 2005 year values. RESULTS: At the time horizon of 20 years, pre-hospital thrombolysis had an average life expectancy of 11.48 years and in-hospital thrombolysis had an average life expectancy of 11.32 years. Total costs were R$ 5640 for pre-hospital thrombolysis and R$ 5816 for in-hospital thrombolysis. In-hospital thrombolysis led an additional cost of R$ 176 per patient. Pre-hospital thrombolysis led an additional 0.15 years of life-expectancy gained compared with in-hospital thrombolysis. CONCLUSION: This model suggests that, from National Health System perspective, implementing pre-hospital thrombolysis for ST-elevation myocardial infarction (STEMI) may lead to extra survival and less cost than in-hospital thrombolysis.