The risk of venous thromboembolism (VTE) associated with low-dose combined oral contraceptive (OC) use has been estimated at 15-30 cases/100,000 women-years. This risk increases in women with thrombophilias associated with antithrombin III, protein deficiencies, and Factor V Leiden (FVL) mutation. Under debate has been whether all women, or at least those with a family history of VTE in a first-degree relative, should be screened for thrombophilia before OCs are prescribed. This article considers two assessment models salient to this debate. The first model considers family history and hereditary thrombophilia based on data from several epidemiologic studies. It suggests that screening 1 million women would result in the detection of 41,080 women with a hereditary thrombophilia; of these, 92 would experience VTE, and there would be 0.92 associated deaths. Screening of 1 million women with a family history of VTE would result in the identification of 672 VTE cases, with a fatality rate of 6.7/year. The second model, based on data concerning FVL mutation, also failed to provide support for the efficacy of a thrombophilia screening program. Women with a family history of thrombophilia, nonetheless, should be offered the option of screening and urged to use an alternative contraceptive method if a thrombophilia is detected.