OBJECTIVE: Our purpose was to compare the multiple-marker screening test with elective amniocentesis for the detection of fetal Down syndrome and other aneuploidies in women aged ≥35. STUDY DESIGN: Our database included the multiple-marker screening test (maternal serum α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and maternal age) and genetic amniocentesis results from 1942 women aged ≥35. A Down syndrome risk ≥1:190 was considered screen positive. An algorithm to detect trisomy 18 was also used. RESULTS: The multiple-marker screening test Down syndrome screen-positive rate was 26.1% ( 507 1942). The Down syndrome detection rate was 75% ( 33 44); the trisomy 18 detection rate was 75% ( 3 4). However, the multiple-marker screening test detection rate for all aneuploidies was only 61%. Missed aneuploidies included trisomy 21, sex chromosome abnormalities, trisomy 13, trisomy 22, and trisomy 18. CONCLUSIONS: The multiple-marker screening test fails to detect approximately 39% of all fetal aneuploidies in women aged ≥35. These data should be provided to women considering prenatal diagnosis so that they can make an informed decision regarding the multiple-marker screening test versus amniocentesis for advanced maternal age. © 1995.