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Objective To analyze the causes and solutions of ABO forward and reverse grouping discrepancy, and to ensure the safety of blood transfusion in clinical. Methods Samples from 75 patients with discrepancy between forward and reverse grouping in December 2019 and March 2022 were tested and analyzed in combination with saline method(forward and reverse grouping), direct antiglobulin test, antibody screening, antibody identification, increasing plasma volume, incubation enhancement test at 4℃, absorption-eluation test and molecular biological tests. Results Causes for abnormal reverse typing were as follows : weak antibody in 11 cases(14.67%), unexpected antibody in 19 cases(25.33%), inverted albumin and globulin ratios in 9 cases(12.00%), increased white blood cells in 3 cases(4.00%), inadequate anticoagulation in 3 cases(4.00%), bone marrow transplantation in 2 cases(2.67%), multiple myeloma in 4 cases(5.33%), acute gastrointestinal bleeding in 3 cases(4.00%). Causes for abnormal forward typing were as follows: self-coagulating in 1 case(1.33%), acute leukemia in 7cases(9.34%), post-transplantation in 1 case(1.33%). Causes for abnormal forward/reverse typing: acute leukemia in 1 case(1.33%), condensin syndrome in 1 case(1.33%), autoimmune hemolytic anemia in 6 cases(8.00%), subtype in 4 cases(5.33%). Results of genotying in 7 cases were as follows: B(A) 04 for 1 case, B(A)02 2 cases, AB3 1case, A1 2 cases, and 1case with new genotype. Conclusion For patients with forward and reverse typing discrepancy for ABO blood group, several studying methods, such as clinical/serological tests inquiring, absorption-eluation tests and molecular biological tests, should be combined to ensure blood transfusion safety.