To evaluate the effect of the type of surgical indication on mortality in infective endocarditis (IE) patients who are rejected for surgery. From January 2008 to December 2016, 2714 patients with definite left-sided IE were attended in the participating hospitals. One thousand six hundred and fifty-three patients (60.9%) presented surgical indications. Five hundred and thirty-eight patients (32.5%) presented surgical indications but received medical treatment alone. The indications for surgery in these patients were uncontrolled infection (366 patients, 68%), heart failure (168 patients, 31.3%) and prevention of embolism (148 patients, 27.6%). One hundred and thirty patients (24.2%) presented more than one indication. The mortality during hospital admission was 60% (323 patients). The in-hospital mortality of patients whose indication for surgery was heart failure, uncontrolled infection or risk of embolism was 75.6%, 61.4% and 54.7%, respectively (p < 0.001). Surgical indications due to heart failure (OR: 3.24; CI 95%: 1.99–5.9) or uncontrolled infection (OR: 1.83; CI 95%: 1.04–3.18) were independently associated with a fatal outcome during hospital admission. Mortality during the first year was 75.4%. The mortality during the first year in patients whose indication for surgery was heart failure, uncontrolled infection or risk of embolism was 85.9%, 76.7% and 72.7%, respectively (p = 0.016). Surgical indication due to heart failure (OR: 3.03; CI 95%: 1.53–5.98) were independently associated with fatal outcome during the first year. The type of surgical indication is associated with mortality in IE patients who are rejected for surgical intervention. •Clinical guidelines allow to group patients according to the surgical indication.•Many IE patients are not operated on despite presenting a clear surgical indication.•The type surgical indication may influence the mortality of these patients.•Prevention of embolism, as surgical indication, is associated with lower mortality.•Conversely, CHF is associated with higher short- and long-term mortality.