Introduction- Despite antibiotic and surgical therapy, infective endocarditis (IE) remains a continuing threat even after hospital discharge due to late complications. Aim- Determine incidence causes and predictors of in hospital and late post discharge mortality in patients with IE.Methods- All 155 consecutive patients with Duke definite/possible IE admitted in the period from Feb. /2005 to Oct. /2008 were included. Demographic, clinical, microbiologic, and echocardiographic data obtained during hospitalization was analyzed; survivors at discharge were contacted by telephone, mail, or home visits and were followed in the outpatient clinic.Duration of the follow up ranged from one to five years (mean 29.3 ± 10.9 months). Variables analyzed as potential predictors of in-hospital and late mortality included clinical, microbiological and echocardiographic data.Results- The in-hospital mortality was 38.7% (n=60). Causes of death were heart failure (HF) (23.3%), Sepsis (20%), surgery related (13.3%), Stroke (10%), cerebral hemorrhage (6.6%), pulmonary emboli (5%), sudden death (SCD) (1.7%), hyperkalemia (1.7%), while the cause of death was undetermined in 18.3%. Of the 95 patients discharged; 29 were lost to follow up; the post discharge mortality in the remainder was 18.2% (n=12). Causes of deathwere SCD (25%), cerebral hemorrhage (16.7%), HF (8.3%), surgery related (8.3%), Relapse of IE (8.3%), and undetermined in 33.3%. Mortality in the first 4 months following discharge was highly related to the complications of IE. Predictors of mortality found on univariate analysis were HF (P=<0.001), not performing cardiac surgery (P= 0.001), fulminant sepsis (P=0.002), higher C-reactive protein level (P=0.021), female gender (P=0.037), and systemicembolization (P=0.043). In multivariate logistic regression; female gender was the most powerful predictor of mortality (OR = 5.729; 95% CI, 1.613 to 20.349; p=0.007); followed by HF (OR = 3.717; 95% CI, 1.049 to 13.158; p=0.042). Subgroup analysis didn't show significant differences between the in-hospital and late mortality predictors. Conclusion- IE mortality is high in Egypt. Female gender is the most powerful predictor of mortality, followed by HF. Mortality in early months following discharge was related to the complications of IE; emphasizing the importance of post discharge follow-up.