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To determine whether patients transfused red blood cell (RBC) products according to guideline-specified pretransfusion hemoglobin (Hb) concentrations or for other reasons were more likely to survive their intensive care unit (ICU) stay.An observational study of 375 478 episodes of ICU care, over 5 years, was performed with ICU survival as the primary outcome. Outcomes were analyzed as a function of pretransfusion Hb concentration for groups with distinct transfusion indications while adjusting for potential confounders.This study included all adult patients discharged from 1 of 203 adult ICUs from 32 US health-care systems. The patients were from community hospitals, tertiary, and academic medical centers.Transfusion of allogenic packed RBCs or whole blood was prescribed at the discretion of the treating clinicians.We found that 15% of adult ICU patients are transfused RBC products, and most transfusions for hemodynamically stable patients are administered above the guideline-specified pretransfusion Hb threshold of 7 g/dL. Hemodynamically stable patients transfused below this threshold were significantly more likely to survive their ICU stay than those not transfused (odds ratio [OR] 0.59, 95% confidence interval [CI], 0.43-0.81; P = .001), and patients transfused at thresholds above 9 g/dL were less likely to survive their ICU stay than those not transfused. Patients of the acute blood loss group who were transfused appeared to benefit or were not harmed by transfusion.Conservative RBC product transfusion practices for groups that are targeted by guidelines are justified by outcomes observed in clinical practice. This study provides evidence for the liberal administration of RBC products to critically ill adults with acute blood loss based on association with lower risk of mortality.