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To describe the clinical spectrum of infective endocarditis in critically ill patients and assess the impact of neurologic complications on outcomes.Prospective multicenter observational study conducted from April 2007 to October 2008.Thirty-three intensive care units in 23 university-affiliated and 10 general French hospitals.Two hundred twenty-five patients with definite IE were studied. Factors associated with neurologic complications and predictors of 3-month mortality were identified by logistic regression analysis. Functional outcomes of patients with neurologic complications were evaluated with the modified Rankin Scale.None.Among 198 patients with definite left-sided infective endocarditis, 108 (55%) experienced at least one neurologic complication. These complications were ischemic stroke (n = 79), cerebral hemorrhage (n = 53), meningitis or meningeal reaction (n = 41), brain abscess (n = 14), and mycotic aneurysm (n = 10). Factors independently associated with neurologic complications were (subhazard ratio [95% confidence interval]): Staphylococcus aureus infective endocarditis (1.45 [1.02–2.05]), mitral valve infective endocarditis (1.54 [1.07–2.21]), and nonneurologic embolic events (1.51 [1.09–2.09]). In contrast, health care-associated infective endocarditis had a protective effect (0.46 [0.27–0.77]). Multivariate analysis identified three variables associated with 3-month mortality (odds ratio [95% confidence interval]): neurologic failure, as defined as a Glasgow Coma Scale <10 (7.41 [2.89–18.96]), S. aureus infective endocarditis (3.26 [1.53–6.94]), and severe comorbidities before admission as defined as a Charlson score >2 (3.16 [1.47–6.77]). Among the 106 patients with neurologic complications assessed at follow-up (3.9 [3–8.5] months), 31 (29%) had a modified Rankin Scale score ≤3 (ability to walk without assistance), nine (9%) a modified Rankin Scale score of 4 or 5 (severe disability), and 66 (62%) a modified Rankin Scale score of 6 (death).Neurologic events are the most frequent complications in infective endocarditis patients requiring intensive care unit admission. They contribute to a severe prognosis, leaving less than one-third of patients alive with functional independence. Neurologic failure at intensive care unit admission represents a major determinant of mortality regardless of the underlying neurologic complication.