The incidence, prevention, and treatment of peripheral venous thrombosis were studied retrospectively in 381 patients with malignant glioma. Of 264 patients who did not receive antithrombotic prophylaxis, 97 (36.7%) developed clinical phlebitis confirmed by venography. Sixty-six cases occurred within 6 weeks of craniotomy. By contrast, only 12 (10%) of 117 patients who received intermittent pneumatic pressure to the calves during craniotomy developed phlebitis (4 patients with 6 weeks of the surgery). Of the 109 patients with venous thrombosis, 103 were treated with anticoagulants. Of the 6 patients treated conservatively, 3 died of pulmonary emboli. Intracranial hemorrhage occurred in 1.9% of the patients taking anticoagulants and in 2.2% of those who did not develop phlebitis. We conclude that patients with malignant gliomas have a high risk of developing peripheral venous thrombosis; that antithrombotic therapy reduces the incidence of thrombosis following craniotomy; and that, in patients who develop phlebitis, anticoagulation reduces the risk of pulmonary emboli without increasing the risk of intracranial hemorrhage.