Background <p>Treatment with combined oral contraceptives (COC) is associated with an increased risk of venous thromboembolism. Several changes of coagulant and anticoagulant factors induced by ethinyloestradiol during treatment with COC, have been demonstrated. Thrombin generation is a global test measuring both coagulant and anticoagulant factors, but the effect of COC on individuals starting COC, has not been examined before on the new equipment, ST Genesia. The aim of this project was to examine the effect of COC on thrombin generation on ST Genesia, in individuals before and after starting COC.</p> Methods <p>Twenty-four female participants between 15 and 34 years of age, who were about to start treatment with ethinylestradiol/levonorgestrel-containing COC, were included in the study. Two blood samples were drawn from each of the study subjects, a baseline sample immediately before first COC dose, and a follow-up blood sample approximately 3–4 months after COC start. Standard biochemical analyses as well as standard and special coagulation analyses including thrombin generation on ST Genesia, were performed in all samples.</p> Results <p>Thrombin generation, i.e., endogenous thrombin generation (ETP) and peak increased considerably after COC start, whereas time-to-peak was shortened. Thrombin-antithrombin complexes (TAT), prothrombin fragments (F1 + 2) and sex hormone binding globulin (SHBG) increased, and the coagulation inhibitors tissue factor pathway inhibitor (TFPI), protein S activity and antithrombin decreased slightly after COC start.</p> Conclusion <p>Although the coagulation factors only changed modestly, the global test thrombin generation performed on ST Genesia showed a considerable change after start of COC.</p>