Objective To evaluate the use of second-trimester uterine artery (UtA) Doppler to predict adverse pregnancy outcome in women with extreme levels of fetoplacental proteins used for Down syndrome screening. Methods At a single institution, women screened for Down syndrome were offered second-trimester UtA Doppler examination if they had one of the following on analysis of maternal serum: pregnancy-associated plasma protein-A <= 0.28 multiples of the median (MoM) (1% of screened population), inhibin >= 3.0 MoM (2%), human chorionic gonadotropin >= 4.0 MoM (2%), alpha-fetoprotein (AFP) >= 2.5 MoM (2%), estriol <= 0.5 MoM (1%). Abnormal UtA Doppler was defined as bilateral or unilateral notching or mean pulsatility index >= 1.45. Results Of 240 women studied, 92 (38.3%) had an adverse pregnancy outcome: small for gestational age (either < 10(th) customized centile (SGA(10)) or < 5(th) customized centile (SGA(5))), low birth weight (LBW, < 2.5 kg), preterm delivery (< 37 + 0 weeks of gestation), fetal loss (late miscarriage or stillbirth), placental abruption and gestational hypertension. Of 167 women screened with all five hormones, those with two or more extreme levels (n = 18, 10.8%) were significantly at risk of adverse pregnancy outcome compared with those with only one marker (61.1% vs. 35.6%, P = 0.04). UtA Doppler was abnormal in 20% (32 of 159 women screened) and increased the risk of adverse pregnancy outcome (RR 2.5, 65.6% vs. 26.0%, P < 0.001). SGA(10), SGA(5) and LBW were significantly more common in women with abnormal UtA Doppler (RR 2.98, 56.2% vs. 18.9%, P < 0.001, RR 4.6, 43.7% vs. 9.4%, P < 0.001 and RR 4.4, 31.2% vs. 7.1%, P < 0.001, respectively). Women with normal Doppler examination still had a 26% risk of adverse pregnancy outcome. Conclusions In women with extreme levels of fetoplacental proteins used for Down syndrome screening, an abnormal second-trimester UtA Doppler examination confers a high risk of adverse pregnancy outcome and SGA in particular, but a normal examination does not rule out an adverse pregnancy outcome. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.