In a large, prospective, multicenter investigation of the prophylaxis of deep vein thrombosis (DVT) in patients undergoing elective abdominal, pelvic, and thoracic surgery, 880 patients were randomized into five treatment groups: those receiving (1) dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU; (2) dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 2,500 IU; (3) heparin sodium, 5,000 IU alone; (4) dihydroergotamine mesylate, 0.5 mg alone; or (5) placebo. Treatment was initiated preoperatively and continued twice daily for five to seven days. Daily radiofibrinogen uptake tests revealed the following DVT rates: Dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU, 9.4%; dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 2,500 IU, 16.8%; heparin sodium, 5,000 IU alone, 16.8%; dihydroergotamine mesylate, 0.5 mg alone, 19.4%; and placebo, 24.4%. Dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU, was significantly superior to all other treatments. Adverse drug experiences did not differ significantly between groups and consisted primarily of postoperative bleeding (2% to 3%), injection site hematoma (6% to 12%), and wound hematoma (1% to 3%).