Abstract Introduction Infective endocarditis (IE) is a serious disease with significant in-hospital mortality (15–30%) despite advances in medical and surgical therapy. Aims To perform a clinical characterization of patients undergoing cardiac surgery for IE and to identify factors that predict in-hospital mortality. Methods We retrospectively analyzed 145 patients with IE admitted between January 2006 and October 2017. Results The median age was 72 years. IE was acquired mainly in the community (69%), and involved the native aortic valve in 54% of patients, biological prosthetic valves in 22.1% and mechanical valves in 10.3%. Staphylococcus spp. (31.0%) were the most frequent etiological agents. Cardiac surgery was emergent in 29 patients, urgent in 108, and elective in eight. The main indications were heart failure (57.9%), large vegetations (20%), systemic embolism (17.2%) and valve dysfunction (15.2%). Overall, biological valves were implanted in 62.1% of patients and mechanical valves in 37.2%. A total of 19 patients (13.1%) died. Predictors of mortality were preoperative atrial fibrillation and lower left ventricular ejection fraction, postoperative severe valve regurgitation associated with cardiogenic shock, sepsis, septic shock associated with cardiogenic shock, cardiac tamponade, need for renal replacement therapy and, although without statistical significance, emergent surgery. Conclusions There is a need for better indicators to enable early identification of surgical candidates for IE, implementation of a heart team, and better surgical strategies, including more rapid intervention, more specific postoperative care, and optimal antibiotic therapy.