We analyzed 270 cases of fungal endocarditis (FE) that occurred over 30 years. Vascular lines, non-cardiac surgery, immunocompromise and injection drug abuse are increasing risk factors. Delayed or mistaken diagnosis (82% of patients), long duration of symptoms before hospitalization (mean +/- standard deviation, 32+/-39 days) and extracardiac manifestations were characteristic. From 1988 onwards, 72% of patients were diagnosed preoperatively, compared with 43% before 1988 (P=.0001). The fungi most commonly isolated were Candida albicans (24% of patients), non-albicans species of Candida (24%), Apergillus species (24%), and Histoplasma species (6%); recently-emerged fungi accounted for 25% of cases. The mortality rate was 72%. Survival rates were better among patients who received combined surgical-antifungal treatment, were infected with Candida, and had univalvular involvement. Improvement in the survival rate (from <20% before 1974 to 41% currently) coincided with the introduction of echocardiography and with improved diagnostic acumen. Fungal endocarditis recurs in 30% of survivors. It is recommended that fungal endocarditis be diagnosed early through heightened diagnostic acumen; that patients be treated with combined lipid-based amphotericin B and early surgery; and that patients be followed up for > or =4 years while on prophylactic antifungal therapy.