Background: Prosthetic valve endocarditis (PVE) is characterized by high morbidity and mortality. Diagnosis is a tough challenge. No clear consensus about the management. Studying our patient characteristics would help better management. Aim of the study: To describe characteristics, management strategies and in-hospital outcome of patients with PVE. Methods: The data of 66 patients referred to Kasr Al-Aini IEP between February 2005 till July 2013 with definite diagnosis of PVE was analyzed. Case definition was based upon modified Duke Criteria. Case report forms were analyzed to collect various clinical, laboratories, microbiologic and echocardiographic features. In hospital course and outcome were recorded. Results and conclusion: Among patients referred to Kasr Al-Aini IEP, patients with PVE are characterized by being young, more commonly males, with exceedingly high in-hospital rate of major complications including 40% mortality rate. Staphylococci and fungi are the most common microorganisms in PVE patients (21% and 15% respectively). Echocardiography could detect vegetation(s) in about 90% of patients with paravalvular leak in half of the patients and periannular abscess in about one third of these patients. Surgery is indicated in the majority of PVE patients with a minority of patients who were successfully treated with antimicrobial therapy alone. Independent predictors for in-hospital major complications are: Not obtaining blood cultures before referral (OR: 6.357, 95% CI: 1.436 to 28.146, p = 0.015), inadequate response to medical treatment (OR: 11.378, 95% CI: 1.292 to 100.245, p = 0.028) and admission eGFR below103 ml/min/1.73m2 (OR: 4.559, 95% CI: 1.074 to 19.356, p = 0.04). Independent predictors for in-hospital mortality are: Not undergoing surgery when indicated (OR: 21.242, 95% CI: 3.063 to 147.328, p = 0.002), admission eGFR <103 ml/min/1.73 m2 (OR: 9.672, 95% CI: 1.970 to 47.477, p = 0.005)and early PVE (OR: 7.795, 95% CI: 1.350 to 45.001, p = 0.022).