Objective: The objective of this study is to estimate the expected health outcomes, costs and cost-effectiveness of changing from current practice, where thrombolytic therapy is given in hospital, to paramedic practice where thrombolytic therapy is administered by appropriately trained paramedics (pre-hospital) for STEMI patients. Methods: A decision-analysis microsimulation model was constructed with a 30-day component and a long-term health state transition component. A brief review of the literature was undertaken to obtain data on time-to-needle to populate the model. The primary health outcome was quality-adjusted life years (QALYs); secondary outcomes included cardiac events, procedures and survival. Costs to the Australian healthcare system for the rest of life were taken as the analytical perspective. Results: On average, STEMI patients gain 0.13 QALYs at an additional life-time cost of $343. The incremental cost-effectiveness ratios were $3428 per life-year gained and $2601 per QALY gained. These estimates were robust to changes in a range of assumptions and parameter values. The most important factor was the timeto- needle - the greater the difference between current practice times and paramedic practice times, the greater the health benefits and lower the cost per QALY (and life-year) gained. A key factor in the model was the substantially lower incidence of heart failure from earlier time-to-needle. Importantly, there was little change in the cost per QALY gained for a wide range of ages; thus, there is no argument to limit thrombolysis by paramedics to above or below an age threshold. Conclusions: Paramedics administering thrombolysis can avert some STEMI deaths and the pre-hospital administration of thrombolysis is good value for money.