OBJECTIVE To assess the association of an isolated single umbilical artery with small for gestational age (SGA) and preterm birth. METHODS In this retrospective cohort study, 219 consecutive women carrying a fetus with an isolated single umbilical artery diagnosed during routine second-trimester anatomic survey were compared with 219 women carrying a fetus with a three-vessel cord. Pregnancies with fetal anomalies or aneuploidy were excluded from the analysis. Outcomes included pregnancy-induced hypertension, gestational age at birth, birth weight, SGA, defined as birth weight less than the 10th percentile, and indicated or spontaneous preterm birth, defined as delivery before 37 weeks of gestation. RESULTS In univariable analysis, the presence of an isolated single umbilical artery was significantly associated with lower birth weight (3,146 compared with 3,430 g) and with SGA (11.9% compared with 2.7%; P<.001 for each outcome). The rates of pregnancy-induced hypertension (7.3% compared with 1.8%, P=.01) and indicated but not spontaneous preterm delivery (5.5% compared with 0.9%, P=.01 for indicated and 8.2% compared with 4.6%, P=.12 for spontaneous) were also more common in pregnancies with an isolated single umbilical artery. In multivariable analysis controlling for potential confounders, an isolated single umbilical artery remained associated with SGA, pregnancy-induced hypertension, and medically indicated preterm birth (adjusted odds ratio [OR] 3.97, confidence interval [CI] 1.55-10.12; adjusted OR 3.50, CI 1.10-11.18; adjusted OR 7.35, CI 1.60-33.77, respectively). CONCLUSIONS Pregnancies complicated by isolated single umbilical artery are at increased risk for SGA and pregnancy-induced hypertension but not for spontaneous preterm birth. METHODS II.