This study aimed to evaluate the effect of an increase in nuchal translucency (NT) thickness on the myocardial performance index (MPI) in fetuses without cardiac anomaly in the first trimester and to determine whether a difference in MPI between those with and without trisomy 21 in these fetuses could be determined. The study group consisted of 53 pregnancies complicated with increased NT thickness without any associated structural anomalies. Forty-six gestational age-matched pregnant women whose fetuses had normal NT thickness were enrolled as the control group. In the increased NT thickness group, the mean isovolumetric relaxation time (IRT) value (0.050 ± 0.011 s) was significantly higher and the mean ejection time (ET) value (0.149 ± 0.010 s) was significantly lower than those values in the normal NT thickness group (0.045 ± 0.005 and 0.155 ± 0.009 s, p=0.023 and p=0.009, respectively). We found a significantly higher mean left MPI value in the increased NT thickness group (0.574 ± 0.153) versus the normal NT thickness group (0.487 ± 0.107, p < 0.001). Within the increased NT thickness group, the mean left MPI value was similar in the fetuses with normal karyotype and those with trisomy 21 (p=0.419). We demonstrated a significantly greater mean MPI value in the increased NT thickness group than in the normal NT thickness group. Within the increased NT thickness group, no differences in the left MPI value in the fetuses with normal karyotype and the fetuses with trisomy 21 were found.