Background: Blood cell antigens may cause maternal alloimmunization leading to fetal/newborn disorders. Non-invasive prenatal diagnostics (NIPD) of the blood group permits the determination of feto-maternal incompatibility. Aim: To evaluate 14 years of blood group NIPD at the Institute of Hematology and Transfusion Medicine (IHTM) in Warsaw. Methods: Plasma DNA from 536 RhD-negative, 24 Rhc-negative, 26 RhE-negative, 43 K-negative, and 42 HPA-1a-negative pregnant women was examined by real-time PCR to detect RHD, RHCE*c, RHCE*E, RHCE*C,KEL*01 and HPA*1A, respectively. We tested for CCR5, SRY or bi-allelic polymorphisms and quantified the total or fetal DNA. Results: The results of fetal antigen status prediction by NIPD in all but one case (false-positive result of KEL*01) were correct taking neonate serology as a reference. It was confirmed that all negative results of NIPD contained fetal DNA except for four cases where there was no difference between the parents' polymorphisms. Conclusions: A fetal genotype compatible with the mother was determined in 25% of all pregnancies tested at the IHTM for the fetal blood group. These cases were not at risk of disease, so it was possible to avoid invasive procedures.