While subcutaneous heparin is a standard prophylaxis for death from pulmonary embolism following general surgery, it has been suggested that adding the vasoconstricting drug dihydroergotamine would improve survival compared to heparin alone. Dihydroergotamine may be associated with rare but life-threatening side effects; thus, reduced mortality from pulmonary embolism could be offset by increased mortality from other causes. Because a clinical trial to examine this possibility would be impractical, we performed a cost-effectiveness analysis to evaluate the effects of prophylactic dihydroergotamine on mortality. Based on published data, despite its favorable effects on the prevention of deep vein thrombosis, the addition of dihydroergotamine did not appear to save lives when added to heparin as prophylaxis. Probabilistic sensitivity analysis demonstrated that even if published risk estimates are in error, substantial changes would still not support the conclusion that dihydroergotamine is lifesaving. In the absence of clear potential for improved survival, the increased costs associated with dihydroergotamine provide reason to question its routine prophylactic use in general surgery.