Introduction: Early surgery in prosthetic valve endocarditis (PVE) is frequently emphasized in literature. There are many controversial issues because large randomized studies are lacking, PVE is not very common and PVE defi nition has changed over the time. Objective: To demonstrate the efficacy of medical therapy with antibiotics (MTA) in PVE without complications. Ten years follow up planned. Methods: Retrospective analysis of 247 patients discharged with established endocarditis between January 2000 and December 2004 from N.G. Lupu Hospital and M. Balș Infectious Diseases Institute. Out of 247, 56 patients with possible or definite PVE (modified Duke with Lamas criteria) were divided in two groups: early and late PVE (12 month after surgery cut off ). We evaluate the role of MTA on PVE course. Variables: demographic data, microbial etiology, peripheral site of infection, comorbidities, clinical, biological and echocardiography parameters, MTA regimens and their side eff ects (SE). MTA duration overall was completed up to 6 weeks. Results: Early PVE: 52%, mean age: 55 years, male 64%. Etiology (% Early vs Late): Negative blood cultures 55 vs 48. Comorbidities related to in-hospital death: type 2 diabetes. MTA regimens were frequently changed due to SE (Oxacillin p = .035, Vancomycin p = .005). MTA responders showed no outcome difference between regimens. Imipenem + Amikacin were preferred due to few SE and because of the shorter duration up to fever remission (p = .004), irrespective of causative organism and PVE type. Patients’ outcome: favorable 71%, in hospital death 2%, hospital transfer due to complications 27%. Early valvular surgery was due to perivalvular extension of infection (p < .001); systemic embolism (p = .007); persistent fever (p = .03). In-hospital mortality was related to prosthesis dehiscence favored by annular abscesses (p = .008). Conclusions: Individualized antibiotic therapy efficacy, irrespective of regimen, was successful in early and late prosthetic valve endocarditis without complications. Guideline recommended antibiotic therapy was abandoned due to frequent side effects. Study limitation: impaired statistical power due to small number of patients, many negative blood cultures probably due to initiation of MTA in referring center.