This study highlights a shift towards more restrictive red blood cell (RBC) transfusion practices in a Swiss university hospital from 2012 to 2019, aligning with clinical guidelines and the Choosing Wisely initiative. Analyzing 14,598 hospitalizations with RBC transfusions, researchers found a significant decrease in mean pretransfusion hemoglobin (Hb) levels in both general internal medicine (from 74.0 g/l to 68.8 g/l) and other clinics (from 78.2 g/l to 72.7 g/l). The study also observed a reduction in potentially inadequate transfusions (transfusions at Hb ≥80 g/l) from 26.9% to 5.5% in general internal medicine and from 37.0% to 15.2% in other clinics. Concurrently, there was an increase in the administration of single RBC units. Risk factors for potentially inadequate transfusions included older age, surgery, acute hemorrhage, chronic heart failure, ischaemic heart diseases, chronic pulmonary diseases, malignancy, and rheumatic disease. This research underscores the impact of guideline recommendations on transfusion practices and identifies patient groups that may benefit from targeted interventions to further optimize transfusion decisions.