This study examined whether differential effects of 2 agents commonly used for hemostatic purposes during cardiac surgery, aprotinin and epsilon-aminocaproic acid (EACA), exist with respect to elevations in proinflammatory interleukins (ILs) and matrix metalloproteinases (MMPs) in patients undergoing coronary artery bypass surgery. Sixty patients were prospectively randomized to receive either aprotinin (1 x 10 KIU; n = 30) or EACA (5 g IV; n = 30), and blood samples were obtained for IL and MMP levels just before induction of anesthesia (Baseline), 10 minutes after separation from cardiopulmonary bypass (Post), and 6 hours after surgery (6 hours). IL-6 was increased at Post in the EACA group and increased further at 6 hours. In the aprotinin group, IL-6 was significantly increased only at 6 hours. MMP subtypes associated with inflammation, MMP-8, and MMP-9 were increased in the EACA group at Post and remained elevated at 6 hours. Thus, differential effects on IL and MMP release occurred between aprotinin and EACA, indicative of different mechanisms of action independent of hemostatic effects.