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To determine whether transfusion of red cells either ≤5 days or ≥20 days from donation alters tonometric indexes of gastric mucosal oxygenation or global oxygenation parameters in euvolemic anemic critically ill patients without ongoing hemorrhage. The a priori hypothesis was that stored red cells worsen gastric oxygenation.Prospective, double-blind, randomized study.A 12-bed general medical/surgical intensive care unit in a Scottish teaching hospital.Ventilated euvolemic anemic (mean ± sd hemoglobin, 85.8 ± 8.4 g/L) critically ill patients with significant organ failure, but no evidence of hemorrhage.After baseline measurements, patients were randomized to receive two units of leukodepleted red cells that were either ≤5 days (ten patients) or ≥20 days (12 patients) after donation according to a standardized protocol.Changes in gastric to arterial Pco2 gap (Pg-Paco2 gap), gastric intramucosal pH, arterial pH, arterial base excess, and arterial lactate concentrations were measured during baseline (2.5 hrs), during transfusion (3 hrs), and for 5 hrs after transfusion. Mean age of red cells stored ≤5 days was 2 days (first and third quartile, 2, 2.25; range, 2–3); red cells stored ≥20 days had a mean age of 28 days (first and third quartile, 27, 31; range, 22–32). Hemoglobin concentration increased by 15.0 g/L and 16.6 g/L, respectively, in the fresh and stored groups (p = .62). There were no significant differences between the groups either using treatment-by-time analysis or comparing the pre- and posttransfusion periods either for Pg-Paco2 gap (mean difference, 0.03 kPa; 95% confidence limits, −1.66, 1.72) or gastric intramucosal pH (mean difference, 0.015 pH units; 95% confidence limits, −0.054, 0.084). The mean change within each group from the pre- to posttransfusion period for Pg-Paco2 gap and gastric intramucosal pH, respectively, was 0.56 kPa (95% confidence limits, −0.68, 1.79) and −0.018 pH units (95% confidence limits, −0.069, 0.032) for “fresh” red cells and 0.52 kPa (95% confidence limits, −0.6, 1.64) and −0.033 pH units (95% confidence limits, −0.080, 0.129) for “stored” red cells. There was no statistically or clinically significant improvement in any other oxygenation index during the measurement period for either group compared to baseline values.Transfusion of stored leukodepleted red cells to euvolemic, anemic, critically ill patients has no clinically significant adverse effects on gastric tonometry or global indexes of tissue oxygenation. These findings do not support the use of fresh red cells in critically ill patients.