The most common cause of thrombophilia is a point mutation in factor V gene (G1691A), leading to factor V Leiden synthesis, which is resistant to the inhibition by activated protein C. Administration of oral contraceptives is associated with an increased risk of venous thromboembolism in carriers of factor V Leiden mutation. We describe here a case of 44-year-old woman who developed right popliteal and superficial deep vein thrombosis after a 2-month use of a contraceptive which consists of 0.15 mg levonorgestrel and 0.03 mg ethynylestradiol. The mutation G1691A of factor V gene was detected with the polymerase chain reaction. No other inherited or acquired risk factors for thrombosis was found in this patient. Treatment with low molecular weight heparin and subsequently, oral anticoagulation was effective. Women with factor V Leiden should be discouraged from taking oral contraceptives. Screening for factor V Leiden in these women appears to be useful and contribute to the prevention of thrombosis in risk situations.