<b><i>Objective:</i></b> To assess the reproducibility and feasibility of automated nuchal translucency (NT) measurement (Volume NT©) in comparison to the two-dimensional (2D) manual approach. The Volume NT technique reveals the correct midsagittal plane automatically and measures the NT at the maximum distance with minimal manipulation. <b><i>Methods:</i></b> In this prospective study, 70 patients underwent NT screening. All standard 2D (standard NT) images and 3D volumes were acquired with an Accuvix V20 Prestige. Off-line measurements of the 3D volumes, manual (manual box NT) and automated (Volume NT) were performed by experienced and nonexperienced operators. Intertechnique and intra- and interobserver agreement were evaluated. <b><i>Results:</i></b> Eleven of 70 cases were excluded due to missing data or aberrant position. The Volume NT program was successful in 83.8% of the cases. Acceptable levels of intraobserver agreement were found for all techniques. The Volume NT technique underestimated NT by 0.21 mm (p < 0.0001) in comparison to standard NT. Between-observer agreement for manual box NT was best for the experienced operators. For Volume NT, the results for between-observer agreement were more ambiguous. <b><i>Conclusions:</i></b> The Volume NT program improves standardization of NT measuring. The technique is reproducible and comparable to the 2D manual approach, particularly for inexperienced sonographers. Further technique refinement should reduce any underestimation.