To determine whether the administration of erythropoietin (EPO) early after the onset of ischemia could enhance the preservation of jeopardized myocardium by reperfusion, 236 patients admitted <6 hours after the onset of chest pain indicative of acute coronary syndromes confirmed to be ST-segment elevation acute myocardial infarctions who were treated with tenecteplase to induce coronary thrombolysis were studied. Patients were randomized to standard care or standard care plus the administration of a single dose of EPO 30,000 IU intravenously immediately before the onset of treatment with tenecteplase. The primary end point was enzymatically estimated infarct size. The results indicated that infarct size index was virtually identical in the 2 groups, with a mean +/- SE of 13.2 +/- 0.1 creatine kinase-MB gram equivalents in controls and 12.4 +/- 0.9 creatine kinase-MB gram equivalents in patients treated with EPO. In conclusion, although the early administration of EPO was apparently safe, it did not enhance the preservation of jeopardized ischemic myocardium.