Reoperation after a surgical procedure for prosthetic valve endocarditis (PVE) is often required due to the existence of either septic recurrence or sterile para-prosthetic leak (PL). The aim of this study was to assess the risk to patients of undergoing a second operation after PVE. Thirty-six patients underwent operation for active PVE at our institution. The operative mortality rate was 11.2%. Among the 32 patients discharged, six underwent a second operation (in two cases due to persisting sepsis) and two underwent a third procedure. Multivariate analysis demonstrated increased probability of further operation for: inability to identify the infecting organism (p = 0.005); drug addiction (p = 0.007); existence of annular abscess (p = 0.016); and early occurrence of PVE (p = 0.018). In the case of mechanical prostheses, PVE was not an independent risk factor (p = 0.206). Nonetheless, 58.3% of patients with mechanical prostheses compared with 5.3% of those with bioprostheses showed annular abscesses, while 41.7% of the former versus 5.6% of the latter suffered one or more recurrences.