To compare the DELFIA Xpress and Quantikine ELISA placental growth factor (PlGF) immunoassay platforms by analysing the same set of early first-trimester maternal serum samples from cases with trisomy 21 and euploid controls. Thirty-seven trisomy 21 cases and 243 euploid control serum samples, drawn at 8(+0) to 10(+6) weeks of gestation, were reanalysed by Quantikine PlGF ELISA following original analysis on the DELFIA Xpress platform. PlGF levels increased with gestation in the euploid controls when measured on both platforms, although raw levels were in general lower on the DELFIA Xpress. After conversion to multiples of the median (MoMs), PlGF was increased in trisomy 21 cases when measured on the DELFIA Xpress platform (euploid: 1.00 MoM, trisomy 21: 1.32 MoM, p < 0.0001) but unchanged when measured on the Quantikine ELISA (euploid: 1.01 MoM, trisomy 21: 1.06 MoM, p = 0.84). Discrepancies exist in the measurement of PlGF when performed on these different platforms, which may to some extent contribute to the inconsistencies found in the literature with regard to PlGF in trisomy 21 pregnancies.