BACKGROUND This study analyzed the distribution of Rh serological phenotype in people living in Hangzhou, China, and assessed the necessity of its routine clinical detection and homotypic infusion. MATERIAL AND METHODS Blood donors and patients who might need blood transfusion were enrolled into the study, and ABO and 5 major Rh serological antigens (C, c, D, E, and e) were routinely detected. The consistent ABO and Rh serological phenotype blood was transfused between the blood donors and recipients. Irregular antibodies were screened and identified in patients before the blood transfusion. Then, the transfusion adverse effects were monitored and compared with the previous data in the hospital. RESULTS The phenotypic frequencies of Rh blood groups were D>C>E>c>e. The CCDee was the most common phenotype and CcdEe was the least common. The detection rate of unexpected antibodies gradually increased, while the unexpected antibodies slowly decreased in the Rh system. There was a correlation between the isotypic infusion of 5 Rh antigens and the detection rate of antibodies in the Rh system (R=0.845). The adverse effects of blood transfusion declined from 19.95% in 2011 with just homotypic ABO infusion to 3.098% in 2019 with the transfusion of homotypic ABO and the 5 major Rh serological antigens. CONCLUSIONS The consistency of the transfusion with ABO and 5 significant Rh serological antigens could prevent and decrease the high frequency production of isoantibodies, which is of vital importance in reducing the incidence rate of adverse effects in patients receiving transfusions.