PURPOSE: The optimal duration and intensity of warfarin therapy after a first idiopathic venous thromboembolic event are uncertain. We used decision analysis to evaluate clinical and economic outcomes of different anticoagulation strategies with warfarin. METHODS: We built a Markov model to assess 6 strategies to treat 40- to 80-year-old men and women after their first idiopathic venous thromboembolic event: 3-month, 6-month, 12-month, 24-month, and unlimited-duration conventional-intensity anticoagulation (International Normalized Ratio, 2-3) and unlimited-duration low-intensity anticoagulation (International Normalized Ratio, 1.5-2). The model incorporated age- and sex-specific clinical parameters, utilities, and costs. Using a societal perspective, we compared strategies based on quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. RESULTS: In our baseline analysis, incremental cost-effectiveness ratios were lower in younger patients and in men, reflecting the higher bleeding risk at older ages, and the lower risk of recurrence among women. Based on a willingness-to-pay of <$50000/QALY, the 24-month strategy was most cost-effective in 40-year-old men ($48805/QALY), while the 6-month strategy was preferred in 40-year-old women ($35977/QALY) and 60-year-old men ($29878/QALY). In patients aged >/=80 years, 3-month anticoagulation was less costly and more effective than other strategies. Cost-effectiveness results were influenced by the risks associated with recurrent venous thromboembolism, the major bleeding risk of conventional-intensity anticoagulation and the disutility of taking warfarin. CONCLUSION: Longer initial conventional-intensity anticoagulation is cost-effective in younger patients while 3 months of anticoagulation is preferred in elderly patients. Patient age, sex, clinical factors, and patient preferences should be incorporated into medical decision making when selecting an appropriate anticoagulation strategy.