Background: Early identification of patients with IE who are at high risk of death or complications of IE may offer the opportunity to improve the outcome of this disease. Several studies have demonstrated that among the complications of IE, congestive heart failure has the greatest impact on prognosis; however previous studies on the other factors predicting the prognosis of infective endocarditis have given somewhat conflicting results.Design: The aim of this study was to evaluate prospectively the determinants of hospital outcome of medical treatment of patients with infective endocarditis. It included 117 patients with definitive/possible infective endocarditis admitted to Cairo university hospitals during the period from April 2010 to March 2012. Clinical, echocardiographic, hematological and microbiological parameters were studied for all patients.Results: The mean age was 34.2±11.1 years. Males were more common than females (66.7% versus 33.3%). The most common underlying heart abnormality was rheumatic heart disease (29.9%). The prevalence of community acquired IE was 68.4 %, and of health-care-associated IE (HAE) was 31.6%. The in-hospital mortality was 29.9%. Intracranial hemorrhage during hospitalization, health care associated IE and congestive heart failure were the most powerful predictors of in-hospital mortality. Less powerful predictors were fulminant sepsis, Stroke, persistent bacteremia, high CRP level and high creatinine level at admission. Conclusion: This study shows that intracranial hemorrhage, health care associated infection and heart failure remained the powerful predictors of in-hospital mortality in patients with IE. The MIC testing and routine follow up cultures help in guiding the treatment regimen for patients with culture positive IE.