To investigate the role of oral contraceptives and their interaction with thrombophilia in ischemic stroke, a case-control study on women with a first ischemic stroke when younger than 45 years was carried out. Oral contraceptives doubled the risk of ischemic stroke in the first 6-18 months of use and hyperhomocysteinemia increased the risk by 3.5-fold. Carriers of factor V Leiden or prothrombin G20210A were not found to have a statistically significant increased risk. The risk of ischemic stroke in oral contraceptive users was 13 times higher in women who were also carriers of factor V Leiden and 9 times higher in those who also had hyperhomocysteinemia.