BACKGROUND To investigate the detectability of non-invasive prenatal testing (NIPT) after prenatal screening to detect foetal chromosomal abnormalities in pregnant women at high risk, and the number of foetal abnormalities could be missed by NIPT. METHODS From January 2009 to March 2018, 3,099 pregnant women at high risk for trisomy 21 and 18 according to the results of prenatal serological screening were enrolled in this study. The women underwent amniocentesis at 18-23 weeks, as well as karyotype testing and/or chromosomal microarray analyses (CMA). We assessed the ability of NIPT to detect chromosomal abnormalities. RESULTS In all, 177 (5.7%, 177/3,099) chromosomal abnormalities were identified. These included 129 (72.9%) abnormal numbers of chromosomes, 6 (3.4%) chromosome structural abnormalities, and 42 (23.7%) other abnormalities, including copy number variation, inversions, and chromosome additions/deletions. Of the 177 (70.0%) chromosomal abnormalities, 124 were detected and 53 were missed by NIPT. CONCLUSIONS NIPT could miss 30.0% of the chromosomal abnormalities detected by amniocentesis and cytogenetic testing. This proportion will likely decrease in the future due to further development of NIPT.