Objective To evaluate the effect of traditional Chinese herbal medicine on the prevention of hemolytic disease caused by maternal-fetal blood group incompatibility.Methods A total of 126 Chinese patients with maternal-fetal blood group incompatibility were studied, including 105 cases of ABO type and 21 cases of Rh type incompatibility. The traditional Chinese herbal medicine was used for preventative treatment in 79 cases, and 47 cases served as controls. The prescription consisted of Herba leonuri 500 g, white peony root 180 g, Banksia rose 12 g, root of Chinese angelica 150 g and Rhizomal ligustica 150 g.Results Preventative treatment with traditional Chinese herbal medicine significantly reduced the perinatal mortality rate in cases of Rh type incompatibility, from 50.0% in the control group to 7.7% in the treatment group (P<0.05). There was no death in the cases of ABO incompatibility. The traditional Chinese herbal medicine also decreased the degree of hemolysis. The percentage of severe cases in the control group was 29.8%, while it was 15.2% in the treatment group (P=0.05). The duration of treatment was closely related to the outcomes. In patients who used traditional Chinese herbal medicine for more than 10 weeks, the incidence of severe hemolysis was 8.2%, compared with 38.9% in those treated for less than 10 weeks (P<0.05). The change of serum immune antibody (A and /or B) titers during the treatment was a very important predictive factor for the outcome of the pregnancy.Conclusion Traditional Chinese herbal medicine is effective not only for ABO type but also for Rh type maternal-fetal blood group incompatibility, with no side effects.