Defects in hemostasis are frequently seen in open heart surgery. Strategies should be reviewed about the peri-operative blood loss and conservation of blood here. In this study, comparison among three agents (Aprotinin, Tranaexaemic Acid & Epsilon Amino Caproic Acid) is done to reduce the peri-operative blood loss in open-heart surgery. Ninety male and female patients within 20-60 years of age were selected who underwent conventional cardiac surgery and anesthesia with Cardio-pulmonary-bypass for common open heart surgeries (ASD, VSD, AVR, etc) and randomly divided into three groups 30 patients in each. Group A, B, C was administered Inj. Aprotinin, Tranaexaemic acid & EACA respectively. Perioperative hemodynamic parameters and blood loss in suction bottle & drainage tube were noted until the 3rd POD. Requirement of blood transfusion, heparin, protamine and blood derived products were also noted. Activated clotting time was documented in the perioperative period. Clinically relevant outcome like re-exploration, mechanical ventilation, morbidities, mortality etc were also verified. Data were analyzed and results were calculated with student's T test & ANOVA. The groups were matched regarding recorded peri-operative variables. Peri-operative blood loss is significantly reduced (p< 0.05) both in the Aprotinin and Tranexamic acid groups. Renal dysfunction was reported in 20% of aprotinin patients, 14.29% of tranexaemic acid patients and 18.51% of EACA patients. A conclusion was drawn from the study that Tranexamic acid can significantly reduce the peri-operative blood loss in open heart surgery cases and that it can be preferred as an agent of choice in blood conservation strategy in these cases.