BACKGROUND: Enterococcal infective endocarditis (EIE) represents a growing proportion of infective endocarditis (IE) cases, particularly among elderly and comorbid patients. EIE poses diagnostic and therapeutic challenges, notably regarding optimal antimicrobial therapy and surgical decision-making. We aimed to compare the clinical characteristics, management, and outcomes of EIE versus non-enterococcal IE (NEIE) in the ESC-EORP EURO-ENDO registry. METHODS: This ancillary analysis of the prospective EURO-ENDO registry included adult patients with definite or possible IE enrolled between January 2016 and March 2018. Patients with monomicrobial EIE were compared with those with NEIE. Clinical, microbiological, imaging, and therapeutic data were analyzed. Multivariable logistic regression including EuroSCORE II and valve status identified independent predictors of in-hospital mortality. RESULTS: Among 3 083 patients, 365 (12 %) had monomicrobial EIE. Compared with NEIE, EIE patients were older (mean 68 vs 58 years), had more comorbidities, and more frequent prosthetic valve involvement (41 % vs 26 %). Aortic valve localization and colonic uptake on PET/CT were also more common. In-hospital mortality was similar (16 % vs 17 %). After adjustment for EuroSCORE II and valve status, EIE was not independently associated with higher in-hospital mortality (adjusted OR 0.67 [95 % CI 0.42-1.04]; p = 0.083). Among 195 EIE patients with one-year follow-up, recurrence occurred in 6 %. Healthcare-associated acquisition, prosthetic valve infection, and recurrence were associated with worse outcomes and lower surgical rates. CONCLUSIONS: EIE affects older, high-risk patients. After adjustment for operative risk, mortality was comparable to other etiologies, highlighting the need for tailored diagnostic and therapeutic strategies.