Background Bleeding in endoscopic sinus surgery (ESS) may increase the risk of intraoperative complications and is associated with poorer outcomes Antifibrinolytic agents have been shown to reduce bleeding if administered systemically. The aim of this study was to determine the effect of topical epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) on bleeding in the surgical field during ESS. Methods A prospective blind randomized controlled trial was performed. Thirty patients undergoing ESS were randomized to receive either 2.5 g of EACA, 100 mg of TA, or 1 g of TA while the contralateral side received saline. The solution was applied as a spray at the conclusion of operating on each side. Bleeding was documented using standardized videoendoscopy and grading scales. Results EACA did not show a significant effect on intraoperative bleeding. TA at 100 mg showed a clinically significant improvement in the surgical field at 2, 4, and 6 minutes after application. The mean for 2 minutes was TA, 1.6 ± 1.08, and control, 2.2 ± 1.3; at 4 minutes was TA, 1.25 ± 1.2, and control, 1.7 ± 1.2,; and at 6 minutes was TA, 0.75 ± 1.2, and control, 1.3 ± 1.4 (p < 0.05). TA at 1 g also approached significance at all time points. Combined results from the two TA groups showed a significant improvement in the surgical field at 2, 4, 6, and 8 minutes after application. TA was regarded by the blinded surgeon as more effective than saline in 80% of cases. No adverse effects were encountered after topical application of either drug. Conclusion Topical application of TA is effective in achieving hemostasis and improving the surgical field. In contrast to EACA, TA is a valuable tool in ESS that merits additional evaluation.