A number of methods of prophylaxis can reduce the likelihood of postoperative deep-vein thrombosis in patients undergoing major orthopedic surgery. Using techniques of decision analysis, we examine the cost-effectiveness of several of these—warfarin sodium, low-dose subcutaneous heparin sodium, graduated compression stockings, intermittent pneumatic compression, heparin plus dihydroergotamine mesylate, and heparin plus stockings—compared with clinical diagnosis and treatment only. Our results show that 153 deaths per 10 000 patients occur when no prophylaxis is used; with most prophylaxes, this number is at least halved, and the most effective methods may reduce the number of deaths by three fourths. In addition, all of the prophylaxes considered are cost saving: average costs of care (including prophylaxis costs) are reduced by $19.40 to $181.60 per patient. Prophylaxis against deep-vein thrombosis in major orthopedic surgery therefore saves both lives and health care dollars.