In acute myocardial infarction, early identification of patients at a high mortality risk is important for planning further therapeutic strategies. Previous studies have demonstrated that the extent of early resolution of ST-segment elevation may represent a simple, quick and noninvasive assessment to identify high risk groups of patients. In a subgroup of the COBALT Study population (Continuous Infusion vs Double Bolus Administration of Alteplase), ST-segment elevation was measured before and 90 to 120 minutes after treatment with alteplase. The subgroup of n = 1,760 patients was not different from the total COBALT population of n = 7169 patients regarding most clinical parameters except Killip Class before treatment. However, the overall 30-day mortality differed significantly between the main study and the substudy (7.76% vs 3.52%; p < 0.001). Three groups of ST-segment resolution were defined: 1. complete resolution (resolution > or = 70%; 762 patients), 2. partial resolution (< 70% and > 30%; 491 patients), 3. no resolution (< 30%; 507 patients). Mortality rate at 30 days for complete, partial and no resolution of ST-segment elevation was 1.31%, 4.28% and 6.11%, respectively (p < 0.001). While this significant correlation between the extent of ST-segment resolution and mortality could be observed for inferior acute myocardial infarction, it could not be found in patients with anterior acute myocardial infarction. This in part may be due to a selection bias that leads to an extremely divergent mortality rate of anterior acute myocardial infarction in the main study and the substudy (10.1% vs 3.94%; p < 0.0001). Despite this limitation, resolution of ST-segment elevation in acute myocardial infarction after thrombolytic therapy allows to identify patients at a high mortality risk and may help to select patients for early invasive procedures such as PTCA. Patients with complete ST-segment resolution showed a particularly low mortality rate, irrespective of the alteplase regimen used (front-loaded alteplase vs double bolus alteplase).