<b><i>Objective:</i></b> The aims of this study were to test whether the performance of first-trimester placental growth factor (PlGF) in screening for preterm preeclampsia (PE) is gestational age dependent and to assess the value of serial first-trimester PlGF measurements in discriminating women at risk for PE. <b><i>Methods:</i></b> PlGF was measured in women with singleton pregnancies at their first antenatal visit at 8+0 to 10+6 and additionally at 11+0 to 14+0 weeks of gestation. The difference in absolute values of serial PlGF measurements was expressed as &#x0394;-PlGF. Values were compared between pregnancies with normal outcome and those complicated by PE. <b><i>Results:</i></b> A total of 814 pregnancies were included, 18 (2.19%) developed PE that required delivery before 37 weeks of gestation. PlGF increases significantly from 8 to 14 weeks of gestation (&#x03C1; = 0.63; <i>p</i> < 0.0001) in normal pregnancies, but not so in preterm PE (&#x03C1; = 0.034; <i>p</i> = 0.893). PlGF discriminates between PE and uneventful pregnancies only after 10 weeks of gestation. &#x0394;-PlGF was significantly lower in PE 5.3 (-1.1 to 9.3) pg/mL compared to uneventful pregnancies 17.3 (9.8-26.0) pg/mL (<i>p</i> = 0.0011). <b><i>Conclusion:</i></b> The discriminatory accuracy of PlGF increases from 10 to 14 weeks of gestation, and serial PlGF measurements might be of particular interest in PE screening.