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Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015–2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%–19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95–0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05–1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01–1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97–0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16–22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters. [ABSTRACT FROM AUTHOR]