Objective: To determine if a false-positive trisomy 18 multiple-marker screening test (all three analytes low: maternal serum alpha-fetoprotein [AFP] at most 0.75 multiples of the median [MoM], unconjugated estriol at most 0.60 MoM, and hCG at most 0.55 MoM) indicates increased risk for obstetric complications or is related to maternal weight. Methods: We accessed our genetic database to obtain multiple-marker screening test results, fetal karyotypes, and pregnancy outcomes from all patients with a normal multiple-marker screening test (n = 3900) and from all patients with a positive trisomy 18 screening test (n = 103) seen in the prenatal diagnosis clinic from 1992 to 1996. During this period, only maternal serum AFP was adjusted for maternal weight. Results: A positive trisomy 18 screen identified five of 12 trisomy 18 fetuses. Women with a false-positive trisomy 18 screen were heavier (175.6 ± 43.8 lb versus 159.9 ± 37.9 lb, P < .001) and younger (29.7 ± 6.5 years versus 32.3 ± 6.5 years, P < .001) than women with a normal multiple-marker screening test, but were not at increased risk for pregnancy complications. Weight-adjusting all three analytes reduced the false-positive trisomy 18 screen rate by 42% (from 1.9% to 1.1%) but did not change the trisomy 18 detection rate. Conclusion: A false-positive trisomy 18 screening test does not indicate increased risk to develop pregnancy complications and may be related to inadequate correction for increased maternal weight.