BACKGROUND: Patient blood management (PBM) programs are associated with improved patient outcomes, reduced transfusions and costs. In 2008, the Western Australia Department of Health initiated a comprehensive health-system-wide PBM program. This study assesses program outcomes. STUDY DESIGN AND METHODS: This was a retrospective study of 605,046 patients admitted to four major adult tertiary-care hospitals between July 2008 and June 2014. Outcome measures were red blood cell (RBC), fresh-frozen plasma (FFP), and platelet units transfused; single-unit RBC transfusions; pretransfusion hemoglobin levels; elective surgery patients anemic at admission; product and activity-based costs of transfusion; in-hospital mortality; length of stay; 28-day all-cause emergency readmissions; and hospital-acquired complications. RESULTS: Comparing final year with baseline, units of RBCs, FFP, and platelets transfused per admission decreased 41% (p<0.001), representing a saving of AU$18,507,092 (US$18,078,258) and between AU$80 million and AU$100 million (US$78 million and US$97 million) estimated activity-based savings. Mean pretransfusion hemoglobin levels decreased 7.9 g/dL to 7.3 g/dL (p<0.001), and anemic elective surgery admissions decreased 20.8% to 14.4% (p=0.001). Single-unit RBC transfusions increased from 33.3% to 63.7% (p<0.001). There were risk-adjusted reductions in hospital mortality (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.67-0.77; p<0.001), length of stay (incidence rate ratio, 0.85; 95% CI, 0.84-0.87; p<0.001), hospital-acquired infections (OR, 0.79; 95% CI, 0.73-0.86; p<0.001), and acute myocardial infarction-stroke (OR, 0.69; 95% CI, 0.58-0.82; p<0.001). All-cause emergency readmissions increased (OR, 1.06; 95% CI, 1.02-1.10; p=0.001). CONCLUSION: Implementation of a unique, jurisdiction-wide PBM program was associated with improved patient outcomes, reduced blood product utilization, and product-related cost savings.