Background: Data about the distribution of ABO and RhD blood groups is important for effective blood utilization, which is maintained by identifying the most clinically required blood type. However, there is a scarcity of data in Ethiopia about the distribution of ABO and RhD blood groups among blood-transfused patients, particularly in the study area.Objective: To determine the frequency of ABO and RhD blood groups among blood transfused patients at Dessie Comprehensive Specialized Hospital, Northern Ethiopia, 2023.Method: A hospital-based retrospective study was conducted from September 1 to September 30, 2022, to determine the frequency of ABO and RhD blood groups among blood-transfused patients at Dessie Comprehensive Specialized Hospital. The study was conducted on data from blood transfused patients from October 2019 to June 2022. A total of 3762 blood transfused patients' data was collected from the blood transfusion log book records. The data were coded, entered, and cleaned using Epi-data version 4.6 and analyzed for descriptive statistics using Stata version 14.0.Result: A total of 3762 blood-transfused patients were included in the study. Of those, females made up 57.3 % (2156/3762). Of 3762 blood transfused patients, the majority (33.9 %, 1277/ 3762) had ABO blood group B, and 81.3 % (3060/3762) of the blood transfused patients were RhD-positive. Eight thousand three hundred fifteen units of whole blood were transfused to 3762 patients, with a mean of 2.2 units of blood transfused per patient. Furthermore, the majority of the study participants 42.82 %, (1611/3762) were given two units of blood, and 8.77 % (330/ 3762) were given four units of blood.Conclusion: Most of the study participants had B and RhD-positive blood groups. The majority of the blood transfused patients were females. Most of the blood was transfused in the medical ward, and whole blood was transfused for all patients.