Introduction: Thyroidectomy is one of the most common surgeries that can be accompanied by postoperative hematoma. The present study aimed to evaluate the impact of the Trendelenburg position on the homeostasis of the surgery site during and after thyroidectomy. Methods: This clinical trial was performed on 60 euthyroid patients in the age range of 18-70 years within 2019-2021. Patients were randomly assigned to the two groups of routine surgery and Trendelenburg using a table of random numbers. The primary outcome was the number of bleeding points immediately after the Trendelenburg position, and secondary outcomes included demographics, final pathology, postoperative hematoma, duration of operation, rate of fluid and seroma accumulation, and patient satisfaction. Data were analyzed in SPSS software (version 19) using Mann Whitney, Chi-square, and Fisher’s exact test. The significance level was set to 5%. Results: The mean age of the patients was 40±13 years, and the majority of them (n=48) were female. The mean number of bleeding points identified intraoperatively was significantly higher in the Trendelenburg group, as compared to that in the routine surgery group (8.7±3.8 vs 5.4±1.8; P<0.001). In the Trendelenburg group, the mean scores of intra-operative blood loss and duration of operation were obtained at 6.4±1.8 g and 118.0±32.0 min, respectively. Conclusion: As evidenced by the obtained results, the Trendelenburg position significantly increased the number of bleeding points in patients undergoing thyroidectomy; nonetheless, it had no effect on the amount of bleeding and operation duration.