During pregnancy, elevated markers of coagulation and fibrinolytic system activation, such as D-Dimer, indicate increased thrombin activity and increased fibrinolysis following fibrin formation. Testing for D-Dimer during pregnancy could therefore be useful for the diagnosis and prediction of a venous thromboembolic event (VTE) or pregnancy-related complications, and for monitoring antithrombotic treatment. This approach, however, is hampered by the fact that even an uncomplicated pregnancy in healthy women is accompanied by a substantial increase of D-Dimer. Thus, prior to clinical application reference values of D-Dimer according to gestational age need to be established. A substantial increase of D-Dimer during pregnancy is seen despite thromboprophylaxis with low molecular weight heparin (LMWH) indicating that further studies are needed to evaluate monitoring of LMWH during pregnancy and to investigate the optimal beginning and dose of LMWH thromboprophylaxis in pregnant women.