This randomized trial compared topical intrapericardial tranexamic acid (TXA) with standard intravenous TXA in 492 adults undergoing cardiac surgery with cardiopulmonary bypass. Topical TXA appeared similarly safe, with fewer composite 30-day adverse events numerically, but it did not meet strict efficacy non-inferiority: red blood cell transfusions and 24-hour drainage were higher. IV TXA remains first-line; topical TXA may suit selected patients who cannot tolerate systemic therapy.