ObjectiveWomen pregnant after oocyte donation (OD) are prone to develop preeclampsia, a syndrome characterised by an aberrant immunologic response, hypercoagulability and endothelial dysfunction. A mediator of inflammation and coagulation is thrombomodulin; a possible role player in this syndrome. Our objective is to investigate whether thrombomodulin dysregulation is involved in the development of preeclampsia after OD. DesignCase-control study. SettingWomen who received OD in the LUMC or in the nearby teaching hospitals between 2004 and 2013. Patient(s)A total of 109 placentas of uncomplicated pregnancies (48 naturally conceived, 21 IVF and 40 OD pregnancies) and 16 placentas of OD pregnancies complicated by preeclampsia. Intervention(s)NoneMeasurementsAbundance of thrombomodulin protein and vitamin D receptor (VDR) were determined using immunohistochemistry. mRNA expression was determined using qPCR. Result(s)Placental thrombomodulin protein abundance was lower in OD pregnancies(diffuse pattern in 45%) than in controls(diffuse pattern in 96%;pConclusion(s) Pregnancies conceived through OD lose placental thrombomodulin expression. This loss is associated with an increased coagulation and inflammation, and indicates that endothelial protection is diminished in OD pregnancies, which might be an explanation for the increased risk for preeclampsia. The vitamin D metabolism is dysregulated in OD pregnancies and might be a target for therapy.