PIP: Recent studies suggesting that oral contraceptives (OCs) containing the progestins desogestrel and gestodene are associated with a two-fold increased risk of nonfatal venous thromboembolism (VTE) compared to earlier formulations have raised new issues for clinicians. The increased risk of 20-30 cases of VTE per 100,000 women annually compares with 60 VTE cases associated with pregnancy. Women with a documented history of unexplained VTE should not use OCs, and when there is a family history, physicians should weigh factors such as age of onset of thrombosis in the affected relative, the clinical setting (e.g., after surgery or trauma), and severity of the episode. The effects of OCs on procoagulants and anticoagulants are minor, except in the 5% of women with factor V Leiden mutation. A clotting assay can determine activated protein C resistance and a polymerase chain reaction test can identify the presence of this mutation; however, widespread screening of OC users is not recommended due to the low incidence of factor V Leiden and the low likelihood these women will develop clots. The present state of knowledge about OCs and VTE risk supports the application of informed clinical judgment.