INTRODUCTION: Genome-wide non-invasive prenatal testing (gwNIPT) has screening limitations for detectable chromosomal conditions and cannot detect microdeletions/microduplications (MD) or triploidy. Thickened nuchal translucency (NT) only detects around 10% of these cases. METHODS: A 4-year retrospective study of singleton pregnancies undergoing first-line gwNIPT screening with subsequent CVS or amniocentesis. All MD cases, with or without gwNIPT screening, were also analyzed. RESULTS: Among 919 pregnancies with gwNIPT and invasive testing, 338 had a single chromosomal abnormality, with 9 false negative gwNIPT results (2.9%) and 26 undetectable abnormalities (18 MD, 8 triploidy) (7.7%). Twelve cases had a dual chromosomal abnormality and 4 returned a low-risk gwNIPT result. Only three (9%) of the "missed cases" had a large NT and two of these also had a structural abnormality. Approximately 90% of chromosomal anomalies missed by gwNIPT were detected by invasive prenatal testing indicated by one or more of the following: failed NIPT (9%), low PAPP-A (12%), early growth restriction (37%) and structural anomalies at pre-NIPT, 13- or 20-week ultrasounds (51%). CONCLUSION: Most chromosomal abnormalities missed or unable to be found by gwNIPT are detected due to growth restriction or structural anomalies, not an enlarged NT. Failed NIPT and low PAPP-A concentrations contributed to detection.