The possible association of a single umbilical artery (SUA) with malformations of vascular etiology is investigated in this study. Four hundred twelve fetal and embryonic autopsies showing one or more congenital malformations, collected over 7 years, were reviewed. Microscopic confirmation of a SUA was evident in 20 cases (4.85%). The two subgroups with 2 (nA = 20) or 3 umbilical vessels (nB = 392) were compared with each other, in relation to the frequency of malformations per organ system. In the group of fetuses with congenital malformations, no association was observed between SUA and the incidence of CNS, cardiac, pulmonary, or genital malformations. However, there was a significantly higher incidence of atresia of hollow organs (P = 0.003), renal aplasia (P = 0.034), and limb reduction defects (LRD) (P = 0.0383) when only a single umbilical artery was present. This suggests a possible etiopathogenetic association of SUA with congenital malformations of vascular etiology. Furthermore, the findings of our study suggest that prenatal identification of a SUA warrants a thorough search for atresias, renal aplasia, and LRD-type malformations.