Background: While the number of hospitalized patients in Dutch hospitals has increased since 1997, the demand for red blood cell units (RBCs) has simultaneously decreased. This implies a dramatic change in transfusion practice toward fewer blood transfusions on average per patient. Objectives: In order to explain the RBC reduction, different patient groups (surgical, medical, obstetrical, and specific age groups) were studied retrospectively in relation to RBC use. In addition, the use of combinations of RBCs, fresh frozen plasma, and platelets during a transfusion episode was examined for trends over time. Materials and methods: Data from the PROTON database, containing information on all transfusions in twelve Dutch hospitals in the period 1996–2005, including corresponding patient data (age, diagnosis, treatment, and hospitalizations) and blood unit data (type, amount, and date) were analyzed. Results: The proportion of RBCs used for surgical patients declined from 50% in 1996 to 40% in 2005, whereas medical use increased from 47% to 58% (the remaining 2%–3% went to obstetrical patients). Changes were more marked in the higher age groups. Also, a trend was observed toward the use of only one or two RBCs during a transfusion episode rather than three or more. Among surgical patients who received blood, the use of combinations of blood units, as compared to RBCs only, increased from 32% to 39%. Conclusion: The results suggest a more restrictive transfusion policy for surgical patients as well as an increase in medical indications for transfusion. This fits well with the current focus on more cost-effective transfusion policies.