Computerized physician order entry (CPOE) has the potential for cost containment in critically ill patients through practice standardization and elimination of unnecessary interventions. Previous study demonstrated the beneficial short-term effect of adding a decision support for red blood cell (RBC) transfusion into the hospital CPOE. We evaluated the effect of such intervention on RBC resource utilization during the two-year study period. From the institutional APACHE III database we identified 2,200 patients with anemia, but no active bleeding on admission: 1,100 during a year before and 1,100 during a year after the intervention. The mean number of RBC transfusions per patient decreased from 1.5 +/- 1.9 units to 1.3 +/- 1.8 units after the intervention (P = 0.045). RBC transfusion cost decreased from $616,442 to $556,226 after the intervention. Hospital length of stay and adjusted hospital mortality did not differ before and after protocol implementation. In conclusion, the implementation of an evidenced-based decision support system through a CPOE can decrease RBC transfusion resource utilization in critically ill patients.