An international multidisciplinary panel of 15 experts reviewed 494 published articles and used the RAND/UCLA Appropriateness Method to determine the appropriateness of allogeneic red blood cell (RBC) transfusion based on its expected impact on outcomes of stable nonbleeding patients in 450 typical inpatient medical, surgical, or trauma scenarios. Panelists rated allogeneic RBC transfusion as appropriate in 53 of the scenarios (11.8%), inappropriate in 267 (59.3%), and uncertain in 130 (28.9%). Red blood cell transfusion was most often rated appropriate (81%) in scenarios featuring patients with hemoglobin (Hb) level 7.9 g/dL or less, associated comorbidities, and age older than 65 years. Red blood cell transfusion was rated inappropriate in all scenarios featuring patients with Hb level 10 g/dL or more and in 71.3% of scenarios featuring patients with Hb level 8 to 9.9 g/dL. Conversely, no scenario with patient's Hb level of 8 g/dL or more was rated as appropriate. Nearly one third of all scenarios were rated uncertain, indicating the need for more research. The observation that allogeneic RBC transfusions were rated as either inappropriate or uncertain in most scenarios in this study supports a more judicious transfusion strategy. In addition, the large number of scenarios in which RBC transfusions were rated as uncertain can serve as a road map to identify areas in need of further investigation.