Numerous randomized clinical trials have compared various durations of anticoagulant therapy with a vitamin K antagonist (ie, warfarin) for an initial episode of venous thromboembolism (VTE). Despite major advances in understanding the pathophysiology of thrombosis and its genetic basis, clinical risk factors at presentation have emerged as the primary determinant of recurrence risk. Following a minimum of 3 months of anticoagulant therapy, patients with VTE in association with transient risk factors (eg, major surgery, trauma, pregnancy) have a low annual recurrence risk, while patients without identifiable provocative risk factors have a recurrence risk of approximately 25% at 4 years with the highest annual rates occurring in the first 2 years. Extending warfarin therapy is highly effective in preventing recurrences but is associated with increased rates of major and minor bleeding. Clinical decision making therefore requires individualized assessment of recurrence and bleeding risk, coupled with patient preference. After 3 months of anticoagulant therapy for a first episode of unprovoked VTE, male sex, age older than 65 years, and an elevated D-dimer level 1 month after discontinuing anticoagulant therapy are useful parameters in identifying patients with an increased recurrence risk. The case of Ms W, a woman with unprovoked venous thromboembolism and hemorrhagic event while receiving anticoagulation, is used to illustrate clinical decision making to determine ongoing treatment.