Objective: We sought to investigate the effects of topical applications of aprotinin and tranexamic acid in preventing postoperative bleeding during open heart surgery. Materials and Methods: Thirty patients undergoing open heart surgery with cardiopulmonary bypass were randomized to three different groups. Group 1 ( n = 10 ) received 1000000 KIU aprotinin, Group 2 (n= 10) received 1 gr tranexamic acid and Group 3 ( n = 10) received placebo before closure of the sternotomy. During the first three hours and 24 hours total postoperative blood loss and amount of transfused blood products were recorded. Results: In Group 1, postoperative bleeding rates were 122 ml during first 3 hours, 302 ml during 24 hours and 384 ml total. In Group 2, postoperative bleeding rates were 108 ml during first 3 hours, 305 ml during 24 hours and 393 ml total. In control group, bleeding rates were- 162, 347 and 502 ml, respectively. Needs for transfusion were 4.7 U in the aprotinin group, 5.4 U in the tranexamic acid group and 6.0 U in the control group. Conclusion: Topical application of aprotinin and tranexamic acid reduced postoperative bleeding, but this was not statistically significant. The differences were insignificant for effectiveness between aprotinin and tranexamic acid and for transfusion requirements. Keywords: Open heart surgery, postoperative bleeding, aprotinin, tranexamic acid