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Background Very few studies focused on patients with severe infective endocarditis (IE) and multiple complications leading to Intensive Care Unit (ICU) admission. Studied primary outcomes depended on the series and multiple prognostic factors have been identified. Our goal was to determinate characteristics of patients, in-hospital mortality and independent prognostic factors in an overall population of patients admitted to ICU for a left-sided, definite, active and severe IE. Methods Retrospective study performed in 9 ICUs during an 11-year period. Results Data of 248 patients (mean age = 62.4 ± 13.3 years; 63.7 % male) were studied. Native and prosthetic valves were involved in 195 and 53 patients, respectively. Causative pathogens, identified in 225 patients, were mainly streptococci (45.6 %) and staphylococci (43.4 %). On ICU admission, 127 patients exhibited extra-cardiac involvement. Ninety-five patients had one or more neurological complications, as followed: ischemic stroke (n = 66), cerebral hemorrhage (n = 31), meningitis (n = 16), brain abscess (n = 16), and intracranial mycotic aneurysm (n = 10). Criteria prompting to cardiac surgery appeared during ICU stay for 186 patients and between ICU and hospital discharges in 5 patients. Due to contra-indications, surgery required by IE was only performed during hospitalization in 125 patients. Moreover, surgery was considered adequate according to usual guidelines in 76 of 191 patients with indication(s) of valvular surgery: for patients with surgical procedure considered as emergency (n = 69), 17 surgical procedures underwent within the first 24 h following indication; for patients with urgent surgical indication (n = 102), surgery was performed during the first week following indication in 40 patients; finally, elective surgery (n = 20) was performed for 19 patients. During hospitalization, 103 (41.5 %) patients died. Four independent prognostic factors were identified: SAPS II > 35 (AOR = 2.604; 95 % CI: 1.320–5.136; p = 0.0058), SOFA > 8 (AOR = 3.327; 95 % CI: 1.697–6.521; p = 0.0005), IE due to methicillin resistant Staphylococcus aureus (AOR = 4.981; 95 %CI = 1.433–17.306; p = 0.0115) and native IE (AOR = 0.345; 95 % CI: 0.169–0.703; p = 0.0034). Conclusions Mortality in patients admitted to ICU for left-sided IE remains high, especially in cases of endocarditis due to methicillin resistant Staphylococcus aureus, when organ failures occur and ICU scores are high.