Objective: To examine the association of isolated single umbilical artery (iSUA) confirmed at the mid-trimester anomaly scan and adverse pregnancy outcome and congenital malformations with up to 10 years postnatal follow up. Methods: This retrospective cohort study included 116,501 singleton pregnancies consecutively enrolled in first trimester screening for aneuploidies and mid-trimester anomaly scan at three University Hospitals in the Capital Region of Copenhagen, Denmark. Data from the Danish Fetal Medicine Database (2008–2017) were verified by manually scrutinizing pre- and postnatal records. The main outcomes of interest were intrauterine fetal demise (IUFD), small for gestational age (SGA), preterm delivery, cesarean section and unrecognized pre- and postnatal congenital malformations. Results: In total, 775 pregnancies with iSUA were identified. Isolated SUA were associated with a significantly increased risk of IUFD (OR 4.16, 95% CI 2.06–8.44), SGA < 3^rd centile (aOR 2.41, 95% 1.85–3.14) and SGA < 10^th centile (aOR 1.84, 95% CI 1.53–2.21), but not with preterm delivery or cesarean section. The laterality of the missing artery was not associated with SGA. In total, 4.3% of pregnancies with iSUA had unrecognized congenital malformations. 1.5% with iSUA had congenital cardiovascular malformations, which were considered minor. Conclusion: Isolated SUA is associated with IUFD and SGA, supporting surveillance during third trimester. If, during the mid-trimester scan, the sonographer achieves thorough, extended cardiac views and finds no additional malformation other than SUA, fetal echocardiography seems not to be needed.