Ventricular size discrepancy may be due to a persistent left superior vena cava (PLSVC) in utero. We sought to investigate for differences in cardiac structure measures and hemodynamics between fetuses with isolated PLSVC connected to the coronary sinus (CS) and normal. Fetuses diagnosed with isolated PLSVC in the second and third trimester were enrolled. We defined two groups: group 1, twenty-five fetuses in the second trimester (22-27 W + 6d); group 2, twenty-two fetuses in the third trimester (28-39 W + 6d). Fifty-three fetuses without intra-cardiac or extra-cardiac anomalies and gestation age-matched were divided into normal control groups: group 3, 28 fetuses in the second trimester; group 4, 25 fetuses in the third trimester. Parameters of cardiac structure and hemodynamics were measured, including: left- and right-side heart size, the diameter of foramen ovale, aorta (AO), aortic isthmus and pulmonary artery (PA), and ratios of cardiac structure RV/LV, RA/LA and PA/AO were calculated. Hemodynamic parameters measured included: flow velocity across mitral valve, tricuspid valve and foramen ovale. In the second trimester, the ratio of RV/LV and PA/AO of the PLSVC fetuses was significantly larger than normal, while the AO diameter, aortic isthmus diameter were smaller than normal (P < 0.05). However, in the third trimester, only the ratio of PA/AO of the PLSVC fetuses was significantly larger, and the aortic isthmus diameter was still smaller than normal (P < 0.05). Isolated PLSVC connecting to the CS is associated with differences in cardiac structure size from normal. These differences appear to diminish with gestational age. A dilated CS may have an influence on development of fetal left heart structures.