To evaluate the potential of routine assessment of intracranial translucency (IT) and other posterior brain parameters in the early detection of open spina bifida during the 11 - 14 weeks screening examination. This prospective, multicenter longitudinal study was conducted with the participation of 20 certified DEGUM II or III experts in Berlin, Germany, between June 2010 and October 2013. All pregnant women undergoing a first trimester screening were included in the study and in every patient were the IT, brain stem (BS), cisterna magna (CM), BS to occipital bone distance (BSOB) and BS/BSOB ratio measured. All patients with continuing pregnancy underwent a second trimester scan. Our data was used to develop our own reference ranges. The primary outcome parameter was the presence of open spina bifida. A total of 15 526 women with 16 164 fetuses were examined. Median of the IT was 2.1 mm, of the CM 1.6 mm, of the BS 2.7 mm, of the BSOB 5.5 mm, and of the BS/BSOB ratio 0.49. There were 11 cases with open spina bifida (incidence of 6.8/10 000). The detection rate was 100 % and in all cases of spina bifida, the anomaly was detected either at the first examination (n = 8) or considered suspicious and the lesion then detected a few weeks later (n = 3). Considering individual measurements, however, the detection rate was 18 % with the complete absence of the IT and 45 % with cut-off values. For the CM measurement, the detection rate was 64 % with the absence of the CM and 73 % with cut-off values. The other parameters proved not to be predictive of open spina bifida. In the hands of an expert, open spina bifida can be reliably diagnosed early in gestation during the 11 - 14 weeks screening. The measurement of different parameters of the posterior brain, especially the CM and the use of cut-off values are of tremendous benefit in achieving a high sensitivity in the detection rate.