Background and Objectives.This study was conducted to form a better understanding of the distribution of ABO and Rh types among the population of the north of Asir region in Saudi Arabia and compare the findings to similar studies that were carried out in other parts of the kingdom and the Middle East. Understanding the frequency of different blood types in different populations is imperative. Blood types are essential not only for transfusion therapy but also for the prediction of the outcome of different diseases. The study aims to establish an understanding of the blood group frequency among the residents of the north of Asir region, Saudi Arabia. Additionally, this study was conducted to compare the blood group frequency in the region to that in different parts of the Arabian Peninsula.Subjects and Methods This study was done throughout 1year from January 1, 2020, to December 31, 2020, using samples from 4142 voluntary subjects at the blood bank of King Abdullah hospital, Bisha. Commercially provided ABO and Rh antibodies were used for the standard blood grouping procedure. Results:Our findings have shown that O is the most prominent ABO blood group while AB was the least frequent. The frequency of A blood type was the second high followed by B blood group while positive Rh factor was more common than the negative. A Comparison of our findings to other studies from Saudi Arabia and nations in the Middle East was also discussed.Conclusion:O+ >A+ >B+ > O->AB+> A->B- > AB- is the order of blood groups frequency in our study for males, while in females the order was almost the same except for the last three blood types was as following: >A->B->AB+. AB- on the other hand, was completely absent in female donors. There are some similarities and differences between our findings and that of other studies from the kingdom and other countries. Knowing and understanding the distribution of ABO and Rh types is essential for creating better policies for transfusion interventions and blood banks managements.