The National Institute of Child Health and Human Development (NICHD), the Society for Maternal–Fetal Medicine, and the American College of Obstetricians and Gynecologists (ACOG), cosponsored a workshop on December 16–17, 2004, to discuss the evidence for first-trimester Down syndrome screening and to explore the effects of combining first- and second-trimester screening, given the results of recent U.S. trials. The experts evaluated the evidence for offering first-trimester screening to provide individual risk assessment for Down syndrome. First-trimester screening has been demonstrated to provide efficient Down syndrome risk assessment, with a detection rate of 84% (95% confidence interval 80–87%), which is clinically comparable to the second-trimester quadruple screen at a fixed false-positive rate of 5%. The participants at the workshop concluded that at this time there is sufficient evidence to support implementing first-trimester Down syndrome risk assessment in obstetric practice in the United States, provided that certain requirements can be met. These requirements include training and quality control standards for first-trimester nuchal translucency measurement and laboratory assays, access to chorionic villus sampling, and appropriate counseling regarding screening options.