【Objective】 To analyze the frequency and profile of irregular antibodies in different ethnic groups through screening and identification of irregular antibodies in 67 552 blood recipients in the Affiliated Hospital of Guizhou Medical University. 【Methods】 Irregular antibody screening was carried out in patients with different ethnic groups from August 1, 2016 to July 31, 2019 by microcolumn gel anti human globulin method, and the irregular antibody specificity were identified by panel cells. 【Results】 1)307 out of 67 552 cases were positive for irregular antibody, with the positive rate at 0.45%(307/67 552). Among them, Chuanqing was 1.27%(6/473), Yi 1.15%(4/348), Buyi 1.03%(10/975), Dong 0.58%(3/514), Han 0.44%(273/62 365), Miao 0.42%(5/1 187) and Tujia 0.34%(2/596), with significant differences among nationalities. Irregular antibody detection: the positive rate of female patients(0.56%, 223/41 359) was higher than that of male patients(0.32%, 84/26 193)(P<0.05). The positive rate of patients transfused before(1.22%, 129/10 553) was higher than non-transfusion patients(0.31%, 178/56 999)(P<0.05). The positive rate of female patients with pregnancy history(0.52%, 192/37 176) was higher than non-pregnancy females(0.17%, 7/4 183)(P<0.05). The positive rate increased with age, without any significant differences(P>0.05). The yields of irregular antibodies did not differ by ABO blood groups(P>0.05). 3)The specificity of 307 irregular antibody positive cases involved 7 blood group systems, including Rh system 59.28%(182/307), MNSs system 9.12%(28/307), Kidd system 0.65%(2/307), Duffy system 0.98%(3/307), Lewis system 5.86%(18/307), P system 0.65%(2/307), and Digeo system 0.33%(1/307). In addition, 15.64%(48/307) of autoantibodies, 0.65%(2/307) of cold antibodies and 4.93%(15/307) of unclear antibodies were detected. 4)The distribution of anti-D, anti-C and autoantibodies were statistically significant among the Han, Buyi, Chuanqing, Miao, Yi and Dong nationalities(P<0.05), while the others were similar(P>0.05). 【Conclusion】 The distribution of irregular antibodies in Guizhou is different by nationalities. Routine screening of irregular antibodies for transfused or pregnant patients can increase the safety and efficacy of blood transfusion. Most of the irregular antibodies detected are Rh blood group system. The exposure to irregular antibodies can be reduced by additional detection of blood group antigen other than RhD for blood recipients and donors, as well as the blood transfusion with matched blood group antigens.