To analyze in a large prospective cohort study of low risk pregnancies whether cell-free fetal (cff) DNA in maternal plasma of the second trimester might be associated with the development of preeclampsia, preterm delivery, and small for gestational age.A subset of a large prospective cohort study in serological RhD negative pregnant women with RHD positive fetuses was used. Cff DNA was determined through the detection of RHD specific sequences with real-time PCR.In 611 pregnancies, rates of 7.2% preeclampsia, 1.6% preterm birth ≤32, 2.9% ≤34, and 12.4% ≤37 weeks of gestation, 5.7% of small for gestational age <5th percentile, and 8.2% <10th percentile were observed. For none of these risk groups an association with cff DNA could be established.Cff DNA in maternal plasma of the second trimester was not found to be a marker for an adverse pregnancy outcome in low risk pregnancies.