Background: Since the endoscopic thyroidectomy was firstly reported by H & uuml;scher in 1997, there has been an ongoing debate regarding whether mainstream endoscopic thyroidectomy can be classified as minimally invasive surgery. In this study, we innovatively proposed the endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach (ETSPIA), a novel minimally invasive surgical technique, and compared its efficacy with the well -established transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: We retrospectively analyzed 50 patients who underwent ETSPIA and 50 patients who underwent TOETVA at Beijing Tongren Hospital, comparing their clinical characteristics, operative duration, blood loss, postoperative alterations in parathyroid hormone (PTH) and serum calcium, recovery post -surgery, complications, and follow-up data. Results: The ETSPIA group had a shorter operation time compared to the TOETVA group (243.40 +/- 58.67 vs. 278.08 +/- 78.50 min; P=0.01). The ETSPIA group also had less intraoperative blood loss than the TOETVA group (20.60 +/- 10.58 vs. 33.00 +/- 11.11 mL; P<0.001). More central lymph nodes were dissected in the ETSPIA group compared to the TOETVA group (5.90 +/- 4.72 vs. 3.36 +/- 2.80; P=0.002). However, the difference in the number of positive central lymph nodes dissected was not statistically significant (1.38 +/- 2.33 for ETSPIA vs. 0.94 +/- 1.39 for TOETVA; P=0.26). The ETSPIA group had a shorter length of stay (LOS) compared to the TOETVA group (6.82 +/- 2.02 vs. 8.26 +/- 2.72 days; P=0.003). The alteration in PTH levels 1 day after surgery was less pronounced in the ETSPIA group compared to the TOETVA group (-26.38%+/- 18.43% vs. -35.75%+/- 22.95%; P=0.04). At the 1 -month postoperative mark, the ETSPIA group showed a marginal increase in PTH levels, whereas the TOETVA group exhibited a slight decrease (10.12%+/- 35.4 3% vs. -11.53%+/- 29.51%; P=0.03). Regarding the average percentage change in serum calcium level 1 day after surgery, the ETSPIA group showed a smaller change, though this difference was not statistically significant (-4.79%+/- 5.47% vs. -5.66%+/- 3.90%; P=0.40). Furthermore, the incidence of hoarseness attributable to transient recurrent laryngeal nerve (RLN) injury in postoperative patients was lower in the ETSPIA group compared to the TOETVA group, but this difference did not reach statistical significance (0% vs. 4%; P=0.15). Conclusions: Overall, compared to TOETVA, the ETSPIA is characterized by a shorter operative route, enhanced protection of the parathyroid glands, reduced trauma, and expedited postoperative recovery.