Chronic venous insufficiency is a widespread disease that can often lead to venous leg ulcers. Recent studies report that certain clotting abnormalities, such as anticardiolipin antibodies, are associated with leg ulcers. Although lupus anticoagulant belongs to the antiphospholipid antibodies, its presence in patients with chronic venous insufficiency has not been reported previously. The purpose of our study was to determine the presence of lupus anticoagulant in chronic venous insufficiency patients at a stage with no leg ulcers, and to follow the clinical outcome. In 37 patients with chronic venous insufficiency and in 54 control patients, lupus anticoagulant was evaluated using the Viper Venom Russell's Diluted Test. Lupus anticoagulant was found significantly more often (p < 0.001) in patients with chronic venous insufficiency than in controls. After 4 years, patients with chronic venous insufficiency with lupus anticoagulant were found to develop a venous leg ulceration more frequently compared to those without (p = 0.01), suggesting that lupus anticoagulant may play an important role in the pathogenesis of chronic venous insufficiency.