Fungal prosthetic valve endocarditis (PVE) is an infrequent but serious complication of valve replacement surgery. To examine its long-term outcome, we retrospectively studied 16 patients with 19 episodes of definite fungal PVE. The mean age was 51 years (range, 27-71 yr). Onset of fungal PVE ranged from 8 days to 3.4 years after valve replacement. Candida albicans was the most common (56%) pathogen isolated. A portal of entry was identified in only 25% of the patients; the presence of intravascular catheters (50%) and prior bacterial endocarditis (38%) were leading predisposing factors. Fever (83%) was the most consistent clinical finding. Potentially serious embolic events, particularly strokes (32%), were common at presentation. Transesophageal echocardiography (sensitivity = 100%) was more useful than transthoracic echocardiography (sensitivity = 60%) in detecting lesions due to fungal PVE. Combined valve replacement surgery and amphotericin B (mean total dose of 1.8 g) in 15 patients resulted in an 87% in-hospital survival and 67% overall survival with a mean follow-up of 4.5 years (range, 5 mo to 16 yr). Two patients had 3 late relapses of fungal PVE up to 9 years after the preceding episode. Each relapse was treated with repeat valve replacement and amphotericin B; in addition, oral azole was utilized for chronic suppression, although the efficacy of this strategy remains unproven. Because of the possibility of relapse, long-term follow-up is essential even after surgical and prolonged antifungal therapy.