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Background: To increase the quality of surgery, getting to low levels of perioperative bleeding is needed in mastoidectomy; however, the existing methods have some complications. The aim of this study was to evaluate the effect of intravenous tranexamic acid on bleeding volume and surgeon's satisfaction during mastoidectomy. Methods: In this randomized clinical trial study, 69 patients with indications of mastoidectomy were evaluated. After obtaining informed consent, the patients were divided into two groups randomly. The case group received infusion of remifentanil (0.1 μg/kg/minute) during surgery as well as tranexamic acid (10 mg/kg) at the beginning of surgery. The control group received only remifentanil (0.2 μg/kg/minute) during the surgery. The mean volume of bleeding, hemodynamic parameters and the surgeon's satisfaction were compared between the groups. Findings: The mean bleeding volumes were 62.1 ± 16.6 and 89.0 ± 25.5 ml in the case and control groups, respectively (P < 0.001). The rate surgeon's “great satisfaction” was 82.4% and 40.0% in case and control groups, respectively (P = 0.004). The mean arterial pressure at 30 minutes after the surgery was lower in the cases than the controls (86.4 ± 5.5 vs. 90.4 ± 4.7 mmHg; P = 0.002). Conclusion: Our study showed that the administration of tranexamic acid is associated with lower perioperative bleeding and also increased surgeon's satisfaction. As the mean arterial pressure was lower in these patients, careful monitoring of the blood pressure is necessary during the surgery.