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Prophylactic therapies have demonstrated efficacy in reducing the incidence of deep venous thrombosis (DVT) in neurosurgical patients. Retrospective analysis of patients undergoing neurosurgical procedures at the University of Michigan demonstrated a high incidence (14%) of postoperative DVT among patients with intracranial neoplasms treated with sequential compression device (SCD) prophylaxis alone. Therefore, we investigated the efficacy and safety of the low-molecular weight heparin enoxaparin in preventing DVT in patients with brain tumors. The goal of the study was to compare SCD, enoxaparin, and combined SCD/enoxaparin prophylaxis among patients requiring surgery for treatment of intracranial neoplasms.Eligible patients were randomized to SCD, enoxaparin, or combined therapy. Treatment was initiated before the induction of anesthesia and was continued throughout the hospital stay. Patients were screened for DVT, using duplex imaging, on four occasions in the first 1 month after surgery. The incidences of DVT and serious adverse events were compared between groups using analysis of variance and the Dunnet two-sided t test.Sixty-eight patients completed the study. Postoperative DVT occurred in 3 of 22 (13.6%) SCD-treated patients, 1 of 23 (4.3%) enoxaparin-treated patients, and 4 of 23 (17.4%) SCD/enoxaparin-treated patients. Differences were not statistically significant. Postoperative intracranial hemorrhage did not occur in patients in the SCD-treated group, whereas 5 of 46 patients receiving low-molecular weight heparin suffered clinically significant intracranial hemorrhage. The study was terminated because of the increased incidence of adverse events in the enoxaparin-treated groups.Enoxaparin therapy initiated at the time of anesthesia induction increases postoperative intracranial hemorrhage.