This study aims to explore the effects of tranexamic acid on the coagulation indexes of patients undergoing heart valve replacement surgery under the condition of cardiopulmonary bypass (CPB). One hundred patients who conformed to the inclusive criteria were selected and divided into a tranexamic acid group and a non-tranexamic acid group. They all underwent heart valve replacement surgery under CPB. Patients in the tranexamic acid group were intravenously injected with 1 g of tranexamic acid (100 mL) at the time point after anesthesia induction and before skin incision and at the time point after the neutralization of heparin. Patients in the non-tranexamic acid group were given 100 mL of normal saline at corresponding time points, respectively. Then the coagulation indexes of the two groups were analyzed. The activated blood clotting time (ACT) of the two groups was within normal scope before CPB, while four coagulation indexes including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), and fibrinogen (FIB) had significant increases after surgery; the PT and INR of the tranexamic acid group had a remarkable decline after surgery. All the findings suggest that the application of tranexamic acid in heart valve replacement surgery under CPB can effectively reduce intraoperative and postoperative blood loss.