OBJECTIVE: The purpose of this study was to evaluate the Down syndrome detection rate at a 5% screen positive rate in first-trimester screening for twins. STUDY DESIGN: This was a retrospective study from August 2005 to July 2007 of twins who underwent first-trimester screening with nuchal translucency, nasal bone, pregnancy-associated plasma protein-A, and free beta-hCG. Risks were calculated on the basis of the Fetal Medicine Foundation twin algorithm. The model simulated distributions of unaffected and affected cases at 12 weeks of gestation. RESULTS: Two thousand ninety-four twin pregnancies (4188 fetuses) met the inclusion criteria. The addition of nasal bone to nuchal translucency, pregnancy-associated plasma protein-A, and free beta-hCG increased the Down syndrome detection rate from 79-89% at a 5% screen-positive rate. CONCLUSION: In twins, first-trimester screening with nasal bone is valuable. The improved Down syndrome detection rate can help these high-risk patients with the decision-making process of whether to pursue invasive testing with its associated pregnancy loss risk.