OBJECTIVES: To evaluate and compared the long-term costs and outcomes of four warfarin treatment strategies of CYP2C9, VKORC1, both CYP2C9 and VKORC1 genotype-guided dosing, and standard warfarin dosing among nonvalvular VTE patients in the societal perspective. METHODS: A discrete event simulation model was used to depict patients’ health states as the disease evolves with time, and captured its associated costs (2007 U.S. dollars) and quality of life. Data was extrapolated with the criteria of including VTE patients of age >=18 years on warfarin with INR target of 2-3. Probabilities, costs and humanistic properties were obtained from the literature, HCUP (NIS & SEDD), and the Medicare Reimbursement Schedule databases. Sensitivity analysis was performed for uncertainty parameters in the model. All costs and benefits were discounted at 3%. RESULTS: There was a significant difference in the prevalence of bleeding complication between standard anticoagulation (6.1%) and the genotype –guided of CYP2C9 and VKORC1 groups (<5.8%). The mean cost and QALYs per patients were $14,340 and 8.1251. The genotype-guided warfarin anticoagulation strategies projected higher cost and higher QALYs. However, considering the threshold of $100,000/QALY, VKORC1 genotype-guided was indicated to be cost-effective among all strategies. Sensitivity analysis demonstrated 25% of the replications of both CYP2C9 and VKORC1 genotype-guided strategy to be