Background: Thrombolytic therapy is used in the treatment of a ST segment elevation myocardial infarction (STEMI) to establish reperfusion, reduce infarct size, prevent and treat complication. Coronary care nurses play integral roles in administration of thrombolytic therapy. The study aimed to assess nurse's performance regarding thrombolytic therapy among patients with acute myocardial infarction in cardiac care units at zagazig University Hospitals. Research design: A descriptive design was used. Tool of data collection: A structured interview questionnaire and observational checklist were used to collect data. Study subjects: All available nurses working in intensive cardiac care units at Zagazig University Hospitals and Their total number was 70 nurse Results: Studied nurses' age ranged between 20-50 years with median 30 years, and 82.9% of studied nurses were females. Regarding nurses qualification 40% of studied nurses had diploma degree in nursing sciences and 65.7% of studied nurses hadn't attended previous training course regarding caring of acute myocardial infarction patients and thrombolytic therapy. 78.6% of the studied nurses had unsatisfactory total knowledge about thrombolytic therapy among patients with AMI. More than three quarter 75.7% of studied nurses had unsatisfactory total practice regarding thrombolytic therapy among patients with acute myocardial infarction. The most (91.4%) of the studied nurses' performance was affected by nurses, patients, and work related factors. There was a statistically significant correlation between nurses' knowledge and practice, and between nurses' total practice and demographic characteristics at age and total experience years. Conclusion: Nurses had unsatisfactory level of knowledge and inadequate practice regarding thrombolytic therapy among patients with acute myocardial infarction and the most of studied nurses reported that their performance was affected by nurses, patients, and work related factors. Recommendation: The training program should be geared in particular to the younger nurses with short duration of experience for caring patient with acute myocardial infarction.