Blood conservation strategies have been shown to be effective in decreasing red blood cell (RBC) utilization in specific patient groups. However, few data exist describing the extent of RBC transfusion reduction or their impact on transfusion practice and mortality in a diverse inpatient population. We conducted a retrospective cohort study using comprehensive electronic medical record data from 21 medical facilities in Kaiser Permanente Northern California. We examined unadjusted and risk-adjusted RBC transfusion and 30-day mortality coincident with implementation of RBC conservation strategies. The inpatient study cohort included 391,958 patients who experienced 685,753 hospitalizations. From 2009 to 2013, the incidence of RBC transfusion decreased from 14.0% to 10.8% of hospitalizations; this change coincided with a decline in pretransfusion hemoglobin (Hb) levels from 8.1 to 7.6?g/dL. Decreased RBC utilization affected broad groups of admission diagnoses and was most pronounced in patients with a nadir Hb level between 8 and 9?g/dL (n?=?73,057; 50.8% to 19.3%). During the study period, the standard deviation of risk-adjusted RBC transfusion incidence across hospitals decreased by 44% (p?0.001). Thirty-day mortality did not change significantly with declines in RBC utilization in patient groups previously studied in clinical trials nor in other subgroups. After the implementation of blood conservation strategies, RBC transfusion incidence and pretransfusion Hb levels decreased broadly across medical and surgical patients. Variation in RBC transfusion incidence across hospitals decreased from 2010 to 2013. Consistent with clinical trial data, more restrictive transfusion practice did not appear to impact 30-day mortality.