Aim: Determine the operative benefits of subcapsular infiltration of adrenaline in terms of blood loss and operative time in open and endoscopic thyroid surgery. Materials and methods: Between June 2020 and May 2021, this prospective, randomized study was carried out. All patients underwent total or hemithyroidectomy via an open or endoscopic approach, depending upon the characteristics of the thyroid lesion. During thyroidectomy, approximately 50–60 mL solution of adrenaline with saline was instilled in the subcapsular plane in a dose of 1:150,000 in 30 patients of group I. Only standard thyroidectomy was performed in the other 30 patients in group II. The pathological characteristics, intraoperative (intra-op) factors, clinical effects, and postoperative blood parameters were analyzed. Results: Of the 93 patients who underwent thyroidectomy over the aforementioned time frame, 60 patients—30 from group I and 30 from group II—were included in the study. The mean time taken for total thyroidectomy was 99.14 ± 7.02 minutes (n = 15), group I 94.00 ± 6.52 minutes (n = 8) vs group II 104.29 ± 7.52 minutes (n = 7) (p-value = 0.001). A complete thyroidectomy caused a mean blood loss of 62.06 ± 5.03 mL (n = 15) and group I 56.25 ± 5.18 mL (n = 8) vs group II 67.86 ± 4.88 (n = 7) (p-value = 0.001). The mean time taken for hemi thyroidectomy was 92.84 ± 6.08 minutes (n = 45), group I 87.73 ± 6.40 minutes (n = 22) vs group B 97.96 ± 5.77 minutes (n = 23) (p-value = 0.001). A hemi thyroidectomy resulted in a mean blood loss of 48.64 ± 5.65 mL (n = 45) and group I 42.50 ± 4.82 (n = 22) vs group B 54.78 ± 6.48 (n = 23) (p-value = 0.001). Conclusion: Results from this prospective study suggest that adrenaline infiltration significantly minimizes bleeding and reduces operative time in patients who undergo thyroidectomy. Clinical significance: Adrenaline infiltration makes the handling of the thyroid gland easier for the surgeon. This effective surgical hemostasis ends up in lesser blood transfusions, decreased operative time, and reduced morbidity and mortality for patients. It would help us to use adrenaline regularly during thyroid surgery.