Background: Infective Endocarditis (IE) is an infection of the endocardia surface of the heart, including the valves. Infective endocarditis (IE) is associated with a broad array of complications and successful treatment of IE relies on microbial eradication by antimicrobial drugs. Surgery contributes by removing infected material and draining abscesses. Nurse's performance plays a role in decreasing morbidity and mortality caused by Infected Endocarditis. The aim of this study was to determine the effect of implementing educational program on nurses' performance and clinical outcomes of patients with acute infective endocarditis. Research design: A quasi- experimental design was utilized in this study. Subjects and method: All nurses (50) from coronary care unit at Educational Hospital Tanta University. Three tools were used to collect data: Nurses‟ Structured Interview Scheduled Sheet to assess socio-demographic characteristics of nurses, structured nurses' knowledge interview questionnaire, nurses' observational checklist about Infected Endocarditis Patients, Acute Infective Endocarditis Patients' Clinical outcomes Assessment Tool: include patients' bioSociodemographic Characteristics, Physiological Parameters Assessment Sheet, Self-Reported Pain Assessment and Acute Infective Endocarditis Complications Assessment. Results: the present study revealed that there was a significant improvement in the mean scores of the total level of knowledge and practice immediately and one-month post program implementation at P < 0.05. Less than one third of patient in control group had severe pain on admission and the majority of them had moderate pain after two weeks. Conclusion: Based on the findings of the present study, it can be concluded that, most of the studied nurses had high level of knowledge and majority of them had good practice one month after program than pre implementation of educational program. Also there were statistical significant improvements in physiological parameter, level of pain, length of hospital stay and progression of complications of patients in the study group than the control group. Recommendation: for nurses: upgrading nurses' knowledge about caring of patients with acute infective endocarditis through, encouraging nurses to attend national and international congresses, seminars, symposia and workshops regularly about IE & care of patients with IE. Recommendation for patient, early detection of patient with IE by investigations and early treatment to prevent further complications