Background:Down syndrome is clinically characterized by mental retardation, birth defects, and specific physical features that are identifiable at birth. Mental retardation ranges from mild to severe with most cases showing a moderate level, Aim and objectives:to evaluate the effectiveness the second-trimester soft marker sonography combined with biochemical quadriple test screening for prenatal diagnosis of triosmy 21 in patient with risk factor for down syndrome, Subjects and methods: this is a prospective cohort study that was conducted at Department of obstetrics & Gynecology ,at Benha university hospital, and carried on 800 patients,Ultrasound was done by voluson 2d searching for a number of soft markers, Results:that there is high significant correlation between down syndrome and Hyper echogenic fetal bowel, Nasal bone hypoplasia, Mild ventriculomegally and Thickned nuchal fold . Also there is significant correlation between Down syndrome and Choroid plexus cyst, Intra-cardiac echogenic foci, Single umbilical artery and Mild hydronephrosis, Conclusion:Second‐trimester soft markers, especially a thickened nuchal fold, remain important observations in the detection of Down syndrome by sonography among fetuses had sonographic screening for aneuploidy, Keywords:Down Syndrome, Second‐Trimester, Benha, Soft Markers, Cohort.