- To evaluate perinatal outcome of fetuses with isolated single umbilical artery (SUA), and specifically to examine whether an isolated SUA is an independent risk factor for perinatal mortality. A population-based study was conducted, comparing pregnancies of women with and without SUA. Deliveries occurred between the years 1988-2006, in a tertiary medical center. Multiple gestations, chromosomal abnormalities and malformations were excluded from the analysis. Stratified analysis was performed using multiple logistic regression models to evaluate the association between SUA and perinatal mortality, while controlling for confounders. Out of 194,809 deliveries, 243 (0.1%) were of fetuses with isolated SUA. Fetuses with SUA were smaller (2,844 ± 733 vs. 3,197 ± 530 g, P < 0.001), and were delivered at an earlier gestational age (38.3 ± 3.0 vs. 39.3 ± 2.1 weeks, P < 0.001), when compared with fetuses with normal umbilical vessels. Mothers to fetuses with isolated SUA tended to have a history of infertility treatments (4.5 vs. 1.7%; P = 0.001) when compared with the comparison group. Fetuses with SUA had more complications, including fetal growth restriction (FGR 9.5 vs. 1.9%, P < 0.001), polyhydramnios (11.5 vs. 3.7%; P < 0.001) and oligohydramnios (6.6 vs. 2.2%; P < 0.001). Deliveries of SUA fetuses had higher rates of placental abruption (3.3 vs. 0.7%; P < 0.001), placenta previa (1.2 vs. 0.4%; P = 0.03) and cord prolapse (2.9 vs. 0.4%; P < 0.001). Higher rates of cesarean deliveries were noted in this group (23.9 vs. 12.2%; P < 0.001). SUA newborns had higher rates of low Apgar scores (<7) in one (11.8 vs. 3.7%; P < 0.001) and 5 min (3.5 vs. 0.4%; P < 0.001). Higher rates of perinatal mortality were noted in the SUA group, as compared to fetuses with normal umbilical vessels (6.6 vs. 0.9%, OR 7.78; 95% CI 4.7-13.0; P < 0.001). Using a multiple logistic regression model, controlling for possible confounders, such as FGR, oligohydramnios, polyhydramnios, prolapse of cord, maternal hypertension and diabetes mellitus, isolated SUA remained an independent risk factor for perinatal mortality (adjusted OR = 3.91, 95% CI 2.06-7.43; P < 0.001). Isolated SUA in our population was noted as an independent risk factor for perinatal mortality.