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Red blood cell (RBC) alloimmunization varies across human populations and ethnic groups. We evaluated the characteristics of RBC alloimmunization and compared the risk of alloimmunization in Korean patients with myelodysplastic syndrome (MDS) and liver cirrhosis (LC), two representative diseases in which chronic transfusion is required. In total, 115 MDS patients and 202 LC patients transfused with RBCs between 2013 and 2015 were retrospectively included. Twenty patients (6.3%) were newly alloimmunized (five MDS patients, 4.3%; 15 LC patients, 7.4%). The median number of RBC units transfused in alloimmunized patients was nine (interquartile range, 4–15 units). As the number of transfused RBC units increased, the cumulative risk of alloimmunization was higher in LC than in MDS patients (P= 0.001). The most common alloantibody detected in patients was anti-E (45%), followed by anti-c (17%), anti-e (10%), anti-C (7%), anti-Fy b (7%), and anti-Jk a (7%). The present data indicate the need for matching of extended RBC antigens (Rh, Duffy, and Kidd systems) for chronically transfused patients with MDS and LC in Korea.