BACKGROUND: Ultrasonographic features of the underlying hemodynamic changes in twin-twin transfusion syndrome (TTTS) may be present at the first trimester scan. AIMS: To investigate the value of intertwin discordance in nuchal translucency (NT) thickness and crown-rump length (CRL) to predict TTTS and other adverse outcomes. STUDY DESIGN: Cohort study. SUBJECTS: One hundred and thirty-five unselected consecutive monochorionic diamniotic twin pregnancies. OUTCOME MEASURES: NT and CRL discordance were assessed at 11 to 13(+6) weeks' gestation. Receiver-operating characteristics (ROC) curves were used to determine their predictive ability for the subsequent development of TTTS. RESULTS: TTTS complicated 16/135 (12%) pregnancies. Four other pregnancies were complicated by selective intrauterine growth restriction (sIUGR) and 3 by miscarriage <24 weeks gestation. The median NT discordance was 15% (range 0-37%) in TTTS pregnancies, 13% (12-19%) in those with miscarriage <24 weeks' gestation, 47% (30-50%) in those with sIUGR, and 14% (0-86%) in those without complications. Prediction for subsequent development of TTTS provided by the discordance in CRL, expressed as the area under ROC curve, was 0.52 (95% confidence interval 0.38-0.67), while it was 0.50 for NT discordance (95% confidence interval 0.35-0.64). NT discordance was significantly higher in sIUGR compared to both uncomplicated and TTTS pregnancies (p=0.004 and p=0.003, respectively). CONCLUSION: In an unselected population of monochorionic twin pregnancies, discordance in CRL and NT measured during first trimester scan is not a clinically useful predictor of the subsequent development of TTTS. Therefore, strict ultrasound follow up is recommended for the timely diagnosis of TTTS.