OBJECTIVES: The investigators undertook a systematic, comprehensive analysis of the therapeutic response and clinical outcomes of reperfusion therapy for acute ST-segment elevation myocardial infarction (STEMI) in 5,470 patients from the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 trial. BACKGROUND: Prompt effective reperfusion therapy for acute STEMI may attenuate major myocardial necrosis. METHODS: We prospectively collected sequential electrocardiographs and clinical data. Aborted myocardial infarction (MI) was defined as maximal creatine kinase < or =2x upper limit of normal coupled with typical evolutionary electrocardiographic changes. RESULTS: Of the patients, 727 (13.3%) had an aborted MI, with the highest frequency (25%) occurring in patients treated <1 h after symptom onset. As compared with MI patients, patients with aborted MI more often had complete ST-segment resolution at 60 min (56.3% vs. 30.2%, p < 0.001) and 180 min (61.5% vs. 53%, p < 0.001); they also had smaller infarct sizes based on QRS score at discharge (2.37 vs. 4.62, p <0.001). Mortality in aborted MI patients compared with those who had true MI was 3.9% versus 4.6% at 30-day and 7.0% versus 7.4% at 1-year. The baseline-adjusted mortality was significantly lower in patients with aborted MI (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.63 to 0.92, p = 0.005 for 30-day and OR 0.70, 95% CI 0.50 to 0.98, p = 0.035 for one year). A very low-risk subset was identified with > or =70% ST-segment resolution at 60 min whose 30-day and 1-year mortality was 1.0% and 2.7%, respectively, compared with 5.9% and 9.3% in aborted MI patients with <70% ST-segment resolution at 60 min (all p < or = 0.002). CONCLUSIONS: Prompt fibrinolytic treatment improved the likelihood of aborted MI. The subgroup with complete 60-min ST-segment resolution had the best clinical outcomes.