Objective: First-trimester aneuploidy screening is in transition from the phase of ‘development’ to that of ‘diffusion.’ As with all other technologies, there is risk of diminished performance until newer centers are well experienced. Typically, inexperienced sonographers under-measure nuchal translucency (NT), and experience, training and continual monitoring of data are needed to ensure that measurements do not deviate. Here we assess the impact of systematic under-measurement on abnormality detection. Study Design: Actual NT measurements from 13,887 normal fetuses, 82 with trisomy 21 (T21) and 61 with other abnormalities (OA) with birth outcome data were mathematically modified to show either a 25% or 0.5-mm decrease in measurement. The impact upon sensitivity and screen-positive rates were assessed. Results: Reducing the NT measurements of T21 and OA cases lowers the sensitivity from 81.7 and 70.5%, respectively, to 67.1 and 62.3% (p < 0.01). If normals are correspondingly lowered, then the screen-positive rates are reduced from 6.9 to 2.0 and 2.5%. To maintain the same screen-positive rates and sensitivity, the risk threshold would have to be increased from 1/300 to 1/556. Conclusion: Minor inaccuracies in NT measurements as small as 25% or 0.5 mm will have very significant negative impacts upon abnormality detection, reducing detection rates by 18% (81.7 to 67.1%). Just as it is completely accepted that laboratory measurements require standardization and quality assurance, NT measurements, because they are used in an algorithm, need to be treated with the same rigor. That way the published data from centers that have developed such screening can be applied by other operators at other sites when counseling their patients.