Aprotinin, tranexamic acid, and epsilon-aminocaproic acid are effective for reducing blood loss and transfusions in patients managed with spine surgery. With the exception of aprotinin, the side-effect profiles of these agents have not been shown to cause any substantial morbidity or to increase the rate of thromboembolic events. Epsilon-aminocaproic acid had a greater effect on reducing blood transfusions as the complexity of surgery increased. The surgeon and/or the anesthesiologist should consider the use of antifibrinolytic agents for patients undergoing spinal procedures in which a large amount of blood loss can be expected; however, at the present time, this is not a United States Food and Drug Administration-approved indication for these agents.