Warfarin is the most widely prescribed anticoagulant in the world. Patients who need more than 15 mg per day should be considered warfarin-resistant. Nearly 30 genes have been reported in association with warfarin pharmacogenetics but genetic polymorphisms in the genes encoding CYP2C9 and VKORC1 have been shown to act as the most important determinants of drug dosage requirements. The major enzyme responsible for the metabolism of S-warfarin, the more potent of warfarin's two stereoisomers, is CYP2C9. Warfarin inhibits vitamin K epoxide reductase (VKOR). A 30-year-old woman was referred to our clinic for pulmonary embolism. She was treated with low molecular weight heparin. The warfarin dose was titrated up to 15 mg daily but after one week, the INR (international normalized ratio) was still subtherapeutic level at 1.8. In this paper, we discuss underlying genetic polymorphisms about warfarin resistance.