Aim To compare the efficacy and safety of intravenous thrombolytic therapy using reteplase and urokinase in acute st-segment elevation myocardial infarction. Methods 34 hospitals of Henan province took part in the clinical trials during 4,6 cases with acute st-segment elevation myocardial infarction were selected in all criteria, and were randomized to receive either reteplase(n=178) or urokinase(n=178) in thrombolytic therapy, according to the clinical symptoms, electrocardiogram, myocardial enzymes and heart rhythm to judge reperfusion rate, and observe the rate of cardiovascular events and bleeding events during hospitalization. Bleeding events were classified by global utilization of streptokinase and tissus plasminogen activator for occluded coronary arteries(GUSTO). Results The reperfusion rate of the group with reteplase was 88.6%(156/176) at 2 h after the thrombolysis, higher than that with urokinase 51.1%(91/178)(P<0.001), and the time of reperfusion in reteplase group was 18 min(IC95%11~25) earlier than urokinase group(P<0.001). The total mortality in reteplase group after thrombolysis during hospitalization was 0.6%(1/176), and 3.4%(6/178) in urokinase group(P>0.05);There were no GUSTO severe bleeding events in both groups, and GUSTO moderate bleeding rates in the group of reteplase and urokinase were 1.7%(3/176), 0.0%(0/178)(P>0.05), GUSTO slight bleeding rate was 6.8%(12/176), 2.8%(5/178)(P>0.05) respectively. Conclusion Reteplase has a higher recanalization rate than urokinase, and lower cardiovascular events and bleeding rate, which is a safe and effective thrombolytic drug.