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Background β-thalassemia major is a hereditary disorder of hemoglobin (Hb) that results in defective Hb synthesis, leading to severe chronic anemia. The mainstay of its treatment is lifelong regular packed red cell transfusions associated with iron-chelating therapy. Globally, there is a gap between blood donation and the actual needs of the patients who depend on transfusion. Patients with β-thalassemia major are no exception and have limited access to regular and safe blood transfusions. This study aimed to assess the gap between the demand and supply of blood for transfusion-dependent patients with β-thalassemia major treated at the Hereditary Blood Diseases Center, Al Ahsa, Eastern Saudi Arabia. Methodology This was a retrospective, cross-sectional study conducted at the Hereditary Blood Disease Center, Al Ahsa, Saudi Arabia, including patient data from January 2017 to December 2019. We used Excel 365 from Microsoft Office 2016, version 1706. Results A total of 158 patients were on chronic transfusion. Of the total patients, 65% were adults, while the remaining 35% comprised the pediatric population. The total number of units requested and received during the three-year period was 14,509 and 9,530, respectively, indicating a gap of 4,979 (34%) units. The age of most of the units received was more than 14 days: 36% of those in 2017, 49.9% in 2018, and 61.5% in 2019. Rare blood groups and alloimmunization accounted for