Maternal serum screening for Down syndrome (DS) in twin pregnancies poses difficulties due to a lack of precise biochemical information about each co-twin. The current study attempts, for the first time, to compare two screening methods: nuchal translucency (NT) measurement and serum screening for DS, in twin pregnancies. 60 women with twin pregnancies (study group) underwent both first-trimester NT scanning and mid-trimester triple-marker serum screening, and were followed throughout their gestation. Nuchal translucency measurements were compared with a matched control of 120 singleton pregnancies with a similar ( 2 years) maternal age and fetal crown-rump length (CRL) ( 3 mm). In both analyses, a risk of 1:380, or higher, of having a DS newborn was considered screen positive. Both mean maternal age (31 3 years) and CRL (62 11 mm) were similar in the study and control groups. The median NT measurement expressed as multiples of the median (MOM) for CRL was similar in the study and control groups (0.85 and 0.88, respectively). Based on NT measurements, 5 per cent of the pregnancies in the study group and 2.5 per cent in the control group were defined as screen positive (p=N โข S). Mid-gestation serum screening was associated with 15 per cent and 6 per cent screen-positive rate in study and control groups, respectively (p<0.05). There was a ratio of 1:3 screen-positive rate between first and second-trimester screening tests within the study group. This high false-positive rate results led to 18.3 per cent amniocentesis rate in the study group compared with 7.5 per cent of the control group (p<0.03). Only one co-twin which was picked up by the NT screen was further diagnosed as trisomy 21, and one co-twin with cardiac and neural tube defect was missed by the two screening tests and was later picked up in an anomaly scan. Although the current series is too small to provoke any changes in screening practice, when twin pregnancies are diagnosed, it seems very reasonable to offer them NT measurement. A larger group may be needed to clarify which approach is the most beneficial screening policy for this highly selected group of pregnant women.