Objective: A study was conducted to evaluate the sensitivity of combining a second trimester triple test and targeted ultrasound in order to detect Down syndrome in women undergoing amniocentesis over 35 years of age. Methods: Women over 35 years of age underwent a triple test and an ultrasound examination for chromosomal markers immediately prior to genetic amniocentesis. Results: One thousand and six women were examined. Four hundred and thirty seven were triple test-positive and in 195 cases ultrasonographic abnormalities were observed. Thirteen had Down syndrome and eight had other chromosomal abnormalities. All women with Down syndrome babies were triple test-positive and seven also had ultrasonographic markers. Three of eight women who had babies with chromosomal aberrations other then Down syndrome were also triple test-positive. Conclusions: The use of the triple test as a screening tool in our population would reduce the number of amniocenteses by 60%, while no cases of Down syndrome would be missed. Ultrasonographic markers have added little to this population. Three non-Down syndrome chromosomal abnormalities and two Down syndrome mosaic cases would be missed by this approach.