Background: The optimal hemoglobin threshold for erythrocyte transfusions in critically ill children is unknown. We hypothesized that a restrictive transfusion strategy of using packed red cells that were leukocyte-reduced before storage would be as safe as a liberal transfusion strategy, as judged by the outcome of multiple-organ dysfunction. Methods: In this noninferiority trial, we enrolled 637 stable, critically ill children who had hemoglobin concentrations below 9.5 g per deciliter within 7 days after admission to an intensive care unit. We randomly assigned 320 patients to a hemoglobin threshold of 7 g per deciliter for red-cell transfusion (restrictive-strategy group) and 317 patients to a threshold of 9.5 g per deciliter (liberal-strategy group). Results: Hemoglobin concentrations were maintained at a mean (±SD) level that was 2.1±0.2 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group (lowest average levels, 8.7±0.4 and 10.8±0.5 g per deciliter, respectively; P<0.001). Patients in the restrictive-strategy group received 44% fewer transfusions; 174 patients (54%) in that group did not receive any transfusions, as compared with 7 patients (2%) in the liberal-strategy group (P<0.001). New or progressive multiple-organ dysfunction syndrome (the primary outcome) developed in 38 patients in the restrictive-strategy group, as compared with 39 in the liberal-strategy group (12% in both groups) (absolute risk reduction with the restrictive strategy, 0.4%; 95% confidence interval, -4.6 to 5.4). There were 14 deaths in each group within 28 days after randomization. No significant differences were found in other outcomes, including adverse events. Conclusions: In stable, critically ill children a hemoglobin threshold of 7 g per deciliter for red-cell transfusion can decrease transfusion requirements without increasing adverse outcomes.