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 the administration of thrombolytic therapy. Aim: Assess nurses' performance regarding management of thrombolytic therapy among acute myocardial infarction Patients'. Design: A descriptive research design was used. Setting: This study was carried out at Critical Care Unit, at Cairo University Hospitals, Egypt. Sample: A convenience samples for all available nurses (45) who accept to participate in this study. Tool: Two tools were used to collect study data: Tool I: Nurses' self-administrated interview questionnaire; include two parts: 1. Demographic characteristics for nurses,2. Nurses knowledge questionnaire. Tool II: nurses‟ practice observational checklist. Results: the present study showed that 64.4% of the studied nurses had an unsatisfactory level of knowledge, and (55.6%) of the studied nurses had in-competent level of practice regarding to thrombolytic therapy