Resistance to oral anticoagulant is a rare phenomenon. We report the case of a 32-year-old woman who required anticoagulation due to a deep venous thrombosis. She gradually developed resistance to acenocumarol and warfarin. Although the HPLC (high performance liquid chromatography) method proved satisfactory acenocumarol levels in plasma, therapeutic anticoagulation was not achieved. The mechanisms of resistance are discussed.