The theory that D-dimer level might has a predictive or diagnostic role in preeclampsia needs to be explored. Aim of the study was to evaluate the association between serum D-dimer level and the occurrence of placenta-mediated complications (PMC) in a pregnant population at high risk. A prospective multicenter cohort study including 200 pregnant women was conducted. Serum D-dimer increases throughout pregnancy, with the highest levels at the end of gestation. Serum D-dimer level was similar for women with PMC and with no complication. Serum D-dimer level was not different in women with preeclampsia uncomplicated women. Serum D-dimer level was not different in women with early or late preeclampsia uncomplicated women. This result suggests that serum D-dimer level was not predictive of the PMC occurrence. This corroborates the fact that the origin of PMC based more on immunity than in hemostasis.