Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716 patients with non-fungal IE in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). Patients were enrolled and the data collected from June 2000 until August 2005. We noted that patients with Candida IE were more likely to have prosthetic valves (p < 0.001), short-term indwelling catheters (p < 0.0001), and have healthcare-associated infections (p < 0.001). The reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2%, p = 0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p = 0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p = 0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p = 0.26). New antifungal drugs, particularly echinocandins, were used frequently. These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE.