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Background: Management of major hemorrhage frequently requires massive transfusion (MT) support, which should be delivered effectively and efficiently. We have previously developed a clinical decision support system (CDS) for MT using a multicenter multidisciplinary user‐centered design study. Here we examine its impact when administering a MT. Study Design and Methods: We conducted a randomized simulation trial to compare a CDS for MT with a paper‐based MT protocol for the management of simulated hemorrhage. A total of 44 specialist physicians, trainees (residents), and nurses were recruited across critical care to participate in two 20‐min simulated bleeding scenarios. The primary outcome was the decision velocity (correct decisions per hour) and overall task completion. Secondary outcomes included cognitive workload and System Usability Scale (SUS). Results: There was a statistically significant increase in decision velocity for CDS‐based management (mean 8.5 decisions per hour) compared to paper based (mean 6.9 decisions per hour; p.003, 95% CI 0.6–2.6). There was no significant difference in the overall task completion using CDS‐based management (mean 13.3) compared to paper‐based (mean 13.2; p.92, 95% CI ‐1.2–1.3). Cognitive workload was statistically significantly lower using the CDS compared to the paper protocol (mean 57.1 vs. mean 64.5, p.005, 95% CI 2.4–12.5). CDS usability was assessed as a SUS score of 82.5 (IQR 75–87.5). Discussion: Compared to paper‐based management, CDS‐based MT supports more time‐efficient decision‐making by users with limited CDS training and achieves similar overall task completion while reducing cognitive load. Clinical implementation will determine whether the benefits demonstrated translate to improved patient outcomes. [ABSTRACT FROM AUTHOR]