Background: The productivity and care quality provided by health care employees are closely related to their performance within health care organization. Therefore, it was essential to determine factors having an effect on the professional nurses’ efficiency if the quality of health care delivery was to be enhanced. Aim of the study: Identify factors influencing nurses' performance in administering thrombolytic therapy among patients suffering from acute myocardial infarction at cardiac care units in Zagazig University Hospitals. Subjects and Methods: Research design: A descriptive design was utilized. Subjects: All available nurses who work at intensive cardiac care units at Zagazig University Hospitals and their total number was 70 nurses. Tools of data collection: Tool I: An questionnaire for interviews to assess socio-demographic data and knowledge of nurses, Tool II : Checklist of observations to assess nurses practices, and Tool III: Factors affecting nurses' performance. Results: The age range of the nurses studied varied from 20-50 years with median 30 years, and 82.9% of studied nurses were females. Regarding nurses qualification 40% of nurses had diploma in nursing sciences and 65.7% of nurses hadn't attended any training course regarding caring of AMI patients and thrombolytic therapy. The majority (91.4%) of nurses' performance was influenced by patients, nurses, and work related issues. Conclusion: The majority of studied nurses reported that their performance was influenced by nurses, patients, and work related issues. 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.