Objective: The objective of this study was to determine whether there are any indication-specific variations in risk reduction for fetal Down syndrome after a normal genetic sonogram. Study Design: A second-trimester genetic sonogram was offered to all pregnant women who were at increased risk for fetal Down syndrome (≥1:274) because of either advanced maternal age (≥35 years), an abnormal triple screen, or both. Outcome information included the results of genetic amniocentesis (if performed), the results of pediatric assessment, and follow-up after birth. Normal genetic sonography was defined as the absence of all ultrasound aneuploidy markers. Results: The overall prevalence of fetal Down syndrome in the tested population was 1.41% (53/3753 pregnancies); however, in the presence of normal genetic sonography, the overall prevalence of fetal Down syndrome was 0.21% (7/3291 pregnancies). The overall risk reduction for fetal Down syndrome in the presence of normal genetic sonography was 6.64-fold (95% CI, 3.01-14.62); the overall negative likelihood ratio was 0.15 (95% CI, 0.07-0.33). In the presence of normal genetic sonography, the risk for fetal Down syndrome was reduced by 83% in patients with advanced maternal age, 88% in patients with abnormal triple screen, 89% in patients with abnormal triple screen who were Conclusion: There were no significant variations in the risk reduction for fetal Down syndrome in the presence of normal genetic sonography. Regardless of the indication for testing, the likelihood for fetal Down syndrome was reduced by 83% to 89%. This information will be useful in counseling pregnant women who are at high risk for fetal Down syndrome and who prefer to undergo genetic sonography before deciding about genetic amniocentesis. (Am J Obstet Gynecol 2002;187:1226-9.)