Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether cardiac function is altered in trisomy 21 fetuses. Methods Between December 2003 and June 2009, we performed echocardiography on 46 trisomy 21 fetuses (28 with structurally normal heart and 18 with CHD) and on 191 chromosomally/ phenotypically normal fetuses with a confirmed normal heart (87 with normal NT and 104 with NT ≥ 95th percentile), between 11 and 35 weeks' gestation. Measurements included: E- and A-wave peak velocity, E/A velocity ratio and E/time velocity integral (TVI) ratio over atrioventricular valves; myocardial performance index (MPI); semilunar valve peak velocity and acceleration time; stroke volume (SV); cardiac output; and DV pulsatility index for veins (PIV) at 11-14 weeks' gestation. Data were categorized into three different age groups for analysis (11 to 13 + 6, 14 to 21 + 6 and 22 to 35 weeks' gestation). Results The tricuspid valve (TV) A-wave velocity and aortic valve peak velocity were significantly reduced in trisomy 21 compared with normal fetuses. Other highly significant differences found in trisomy 21 fetuses at 11-14 weeks' were increased TV-E/A ratio and DV-PIV, and decreased pulmonary valve peak velocity. We also observed evidence of left ventricular (LV) systolic dysfunction, reduced SV and increased MPI. After 14 weeks' gestation, the mitral valve A-wave peak velocity and E/TVI ratio were significantly reduced in the trisomy 21 fetuses with normal hearts compared with the controls with increased NT. Conclusions In comparison with controls with normal or increased NT, cardiac function in trisomy 21 fetuses is abnormal irrespective of the presence of CHD. Evidence for cardiac loading (increased preload and afterload) and LV systolic (in the first trimester) and later diastolic dysfunction was observed. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.