Objective To prenatally diagnose HA fetus with different clinical backgrounds. Methods Genetic tests were performed on 15 gravidas subjected for prenatal diagnosis of HA and different methods were employed for diagnosis according to the gestational weeks and clinical data. Amniotic fluid were taken from pregnant women within 23 gestational weeks for direct genotyping and indirect linkage analysis, since these women had probands with clear-cut mutations. Cordocentesis was performed for linkage analysis in pregnant women over 23 gestational weeks with probands whose types of mutation were unknown, while the FⅧ activity tests were carried out simultaneously. For the pregnant women over 23 gestational weeks without proband, cordocentesis was operated for measurement of FⅧ activity and karyotyping, but carriers of hemophilia A could not be detected in these cases. The introns 22 and 1 inversion of F8 gene were identified by long distance-polymerase chain reaction. Nucleotide sequencing was employed if the gene inversion could not be found and linkage analysis of 7 polymorphic markers, including DXS1108, F8Civs13, INTRON22,DXS1073,DXS9901, DXS15, DXS8069 and sex site (Amelo) were applied eventually. Identification of maternal blood contamination must be done before the tests. Results Fifteen samples were identified without maternal blood contamination. Five fetuses were diagnosed with hemophilia A. Meanwhile there were three pregnant women whose cord blood FⅧ activities were less than 1%. One of them was accompanied by trisomy 21; another had inversion mutation in introns 22 of F8 gene; the remaining one was identified with missense mutation in exon 23 (p. Arg2182Cys) of F8 gene. Conclusions Diverse methods should be applied in prenatal diagnosis of hemophilia A with different clinical backgrounds, for the sake of birth defects prevention.