<p>Prenatal prediction of critical coarctation of the aorta remains challenging. Fetal echocardiography in isolated persistent left-sided superior vena cava (IP L-SVC), a benign variant, can mimic suspected coarctation with shared right-to-left ventricular size discrepancy. We sought to describe cardiac deformation in fetuses with IP L-SVC and compare to those with suspected coarctation. We hypothesized that cardiac deformation as measured by global longitudinal strain (GLS) could differentiate fetuses with coarctation from IP L-SVC.&#xa0;This is a single-center, retrospective study of fetuses with IP L-SVC and suspected coarctation. Fetal cardiac deformation analysis was performed using a vendor non-specific software. The primary variable was GLS. Secondary variables were left ventricular ejection fraction, left ventricular end-systolic volume, and left ventricular end-diastolic volume (LVEDV). Mean LVEDV z-score was determined. Interrater reliability was performed. Baseline measures of GLS were performed using a cohort of normal fetuses.&#xa0;Ninety fetuses were analyzed (IP L-SVC n=28, suspected coarctation n=30, normal n=32). Seventeen required surgical repair for coarctation. Fetuses with IP L-SVC and suspected coarctation had lower GLS (p &lt;0.001) and smaller left ventricular size compared to normal (p&lt;0.001). Fetuses who required surgical repair for coarctation of the aorta had the lowest LVEDV. Interrater reliability was poor to moderate.&#xa0;Our study is the first to date that examines strain in fetuses with IP L-SVC compared to suspected coarctation of the aorta. Cardiac deformation in fetuses with IP L-SVC was indistinguishable from fetuses with suspected coarctation of the aorta. GLS proved a poor predictor of postnatal surgical repair in isolation.</p>