The combination of heparin 5000 U and dihydroergotamine 0.5 mg (HDHE) was marketed in the U.S. in 1985 for prophylaxis of postoperative deep venous thrombosis (DVT). This article evaluates the efficacy, safety, and cost of HDHE for abdominal, pelvic, thoracic, and total hip surgical prophylaxis. Although several controlled trials comparing HDHE to minidose heparin (MDH) indicate superior efficacy of HDHE for nonorthopedic surgical procedures, others do not. Differences in study design and insufficient sample sizes may account for the dichotomy. In the U.S. Multicenter Trial, MDH was surprisingly ineffective for preventing radiofibrinogen uptake test-proven DVT. The apparent superiority of HDHE over MDH is therefore questionable. Ergot-related side effects have been minimized in all studies due to careful patient selection. In actual use, the potential for such side effects appears to be increased. Because twice-daily HDHE is no more effective, costs 4-11 times more, and may pose a greater risk than MDH, the authors do not recommend its use for general surgical prophylaxis. HDHE may prove to be useful in patients undergoing total hip replacement.