Three cohorts of patients with the factor V Leiden mutation were recruited independently (heterozygotes, homozygotes and combined thrombophilia). The antithrombotic efficacy of oral anticoagulation and the predictive value for recurrence of an idiopathic as opposed to a precipitated first event were determined. Idiopathic first events occurred at an older age than precipitated events (43 v 26 years, LR = 23.31, P < 0.001). None of the patients had a recurrent event while on warfarin but the median time to recurrence after stopping warfarin was 9 years (95% CI 0.7-17.3 years). The time to recurrence was shorter when the first event was idiopathic as opposed to precipitated (3.5 v 13 years, LR = 4.76, P = 0.029). A calculation of benefit to risk of oral anticoagulation with a target INR of 2.5 does not support the use of long-term therapy in all patients with the factor V Leiden mutation following a first thrombotic event.