Background: Red blood cells (RBCs) transfusions have saved lives and expedited the recovery of illnesses to millions of patients. However, RBCs transfusions carry high risk of life threatening complications and economic burden. Objective: The present study aimed at assessing the appropriateness of RBCs transfusion at one Ministry of Health hospital in Kuwait and to assess the effect of multiple interventions for improving the appropriateness of RBCs utilization. Methods: The present study used one group pre-test post-test quasi experimental design. To assess the appropriateness of RBCs transfusions, 185 records were reviewed in each of pre and post intervention phases. Improvement interventions included involvement of hospital administrators and heads of departments, development of the hospital transfusion guidelines, improvement of participant physicians' knowledge, and improvement of blood transfusion documentation. Results: The present study revealed 22.4% reduction in the total number of RBCs transfusions in the post intervention phase as compared to pre intervention phase. However, low rate of appropriateness of RBCs transfusion in pre intervention phase (40.4%) was encountered which was minimally improved to 46.5% following implementation of multiple improvement interventions. Physicians showed very low compliance with completion of the newly introduced blood transfusion request and consent forms. Conclusion: The appropriateness of red blood cells transfusions at the study hospital is low before and after implementation of the improvement interventions. Documentation of blood transfusion is deficient at the study hospital. It is recommended to strengthen the blood transfusion interventions used in the present study and to implement these interventions in Ministry of Health Hospitals in Kuwait to improve the appropriateness of RBCs transfusions.