During pregnancy, maternal vitamin D insufficiency could increase the risk of preeclampsia. Aim of the study was to evaluate the relationship between vitamin D status and the occurrence of placenta-mediated complications (PMCs) in a population at high risk. A prospective multicenter cohort study of 200 pregnant patients was conducted. The vitamin D level of patients with placenta-mediated complications was lower at 32 weeks compared to uncomplicated pregnancies (P = 0.001). At 32 weeks, the risk of occurrence of PMCs was five times higher in patients with vitamin D deficiency (RR: 5.14 95% CI (1.50-17.55)) compared to patients with normal vitamin D levels. There was a strong, inverse relationship between serum 25(OH)D levels at 32 weeks and the subsequent risk of PMCs (P = 0.001). At 32 weeks, the vitamin D level of patients with late-onset PMCs was lower than the one of patients with early-onset PMCs and of patients without PMCs (P < 0.0001). These results suggest a role of vitamin D in the maintenance of placental performance and therefore in the prevention of the onset of late PMC.