Background: This paper examines the relationship between determinants of blood transfusion sustainability (BTS) that is master production scheduling (MPS) and blood production (BP) of Uganda. The study was founded on four objectives. The study looked at the direct relationship between MPS and the BTS, direct relationship between MPS and BP, direct relationship between BP and BTS. It also assessed how BP mediated the direct relationship between MPS and BTS. The study used a quantitative method. Methods: A survey questionnaire was administered to collect data from 367 staff of regional blood banks and government university teaching hospital blood banks; and 213 were found to be usable. The main analysis was done using structural equation modeling. Results: This study found that MPS had a negative and insignificant relationship with the BTS. The study found that relationship between MPS and BP was positive and significant. The study also found that relationship between BP and BTS was positive and significant. The study concluded that the effect of MPS on BTS was fully mediated by BP. It was recommended that blood banks seeking to achieve transfusion sustainability must understand the sector in which they operate. The various stakeholders in the blood supply chain ie blood banks, hospital blood banks, funding agents, ministry of health, must also integrate to enhance the transfusion sustainability. Blood banks performance measures essentially timely delivery was very critical for saving lives of patients in need of blood. Conclusion: The study has provided a new conceptual framework that investigate the BP mediating effect on the relationship of MPS and BTS, and thus can serve as an incentive for more research to be conducted in this regard of different developing countries. The authors also proposed identifying the effect of other BP factors such as blood donor management and hospital transfusion practices on BTS.