Introduction: Background: Valvular prostheses are well-known as predisposing factors for endocarditis. By cost and mortality, prosthetic valve endocarditis (PVE) still represents a serious complication. Objective: To determine factors that influence prognosis in medically treated patients during hospitalization, receiving various regimen of therapy with antibiotics (TA). Ten years follow up was planned. Methods: Retrospective analysis of 56 patients admitted with possible or definite PVE (modified Duke with Lamas criteria) between January 2000 and December 2004 in “N.G. Lupu” Hospital and “M. Balș” Infectious Diseases Institute. PVE patients were divided in early and late PVE groups (12 month after surgery cut off ). Disease course under TA was evaluated. Variables: demographic data, comorbidities, microbial etiology, clinical, biological and echocardiography parameters, in hospital death, emergency transfers. TA duration overall was completed up to 6 weeks. Results: Early PVE: 52%, mean age: 55, male gender 64%. Etiology (% early vs late): negative blood cultures 55 vs 48. Comorbidities related to prognosis: type 2 diabetes, independent of microbial etiology, and ischemic heart disease. Adverse outcome was related to: persistent fever, PVE related complication (in-hospital death 2%, transferred 27%), perivalvular extension of infection, annular abscesses (p = .002) and prostheses dysfunction (p < .001). Fever control in responders has not been influenced by the type of TA (multivariate analysis). Systemic embolism was related to etiology (p = .005) and worse outcome (p < .001). Left ventricular (LV) systolic dysfunction influenced prognosis only in ischemic patients (p < .001). There were no differences between factors of bad prognosis between PVE groups. Conclusions: Persistent fever, perivalvular extension of infection, prosthesis dysfunction, systemic embolism, type 2 diabetes, LV systolic dysfunction and concomitant ischemic heart disease were related to adverse outcome in our patients. Serial echocardiography and clinical evaluation are necessary to establish patients that need early surgery for infection control.