This study investigates the clinical features and patient outcomes in patients with infective endocarditis (IE) who required surgical intervention at a single center in Tuscany, Italy. The primary endpoint was a composite of major adverse events (MAEs), including all-cause death, hospitalizations, and IE relapses, while the secondary endpoint was all-cause death. A total of 102 patients were enrolled, with an average age of 66 ± 14 years. The study found that IE on prosthesis, IE-associated heart failure (IE-aHF), and embolic events (EEs) were independently associated with MAEs. IE-aHF and EEs were also independently associated with the secondary endpoint of all-cause death. The presence of IE-aHF, CRP at admission, procalcitonin peak, left ventricular ejection fraction (LVEF), abscess, and prosthetic detachment were significant predictors of all-cause death. Kaplan-Meier survival curves confirmed a strong difference in MAE-free survival between patients with EEs and IE-aHF. The study highlights the importance of identifying specific features associated with poor prognosis in high-risk patients with IE.This study investigates the clinical features and patient outcomes in patients with infective endocarditis (IE) who required surgical intervention at a single center in Tuscany, Italy. The primary endpoint was a composite of major adverse events (MAEs), including all-cause death, hospitalizations, and IE relapses, while the secondary endpoint was all-cause death. A total of 102 patients were enrolled, with an average age of 66 ± 14 years. The study found that IE on prosthesis, IE-associated heart failure (IE-aHF), and embolic events (EEs) were independently associated with MAEs. IE-aHF and EEs were also independently associated with the secondary endpoint of all-cause death. The presence of IE-aHF, CRP at admission, procalcitonin peak, left ventricular ejection fraction (LVEF), abscess, and prosthetic detachment were significant predictors of all-cause death. Kaplan-Meier survival curves confirmed a strong difference in MAE-free survival between patients with EEs and IE-aHF. The study highlights the importance of identifying specific features associated with poor prognosis in high-risk patients with IE.