Abstract: Background The clinical application of gasless trans-subclavian approach endoscopic thyroidectomy (GTAET) is gradually increasing, but its safety, thoroughness and popularization should be further investigated. Objective To analyze the clinical efficacy and surgical learning curve of GTAET for unilateral papillary thyroid carcinoma (PTC).Methods The patients with PTC who underwent unilateral radical thyroidectomy in the Department of Thyroid (Hernia) Surgery, the First Medical Center, Chinese PLA General Hospital from January 2023 to December 2023 were retrospectively selected, the patients were divided into the GTAET group and the linea alba cervicalis approach open thyroidectomy (LACAT) group according to the surgical approach. The clinical efficacy indicators including surgical safety, thoroughness, and patient subjective evaluations were compared, and cumulative sum analysis (CUSUM) and best-fit curve analysis was used to analyze the learning curve of GTAET.Results A total of 309 PTC patients were included and grouped according to the surgical approach. There were 60 patients in the GTAET group, including 12 males and 48 females, with an average age of (38.95±8.34) years. The LACAT group included 249 patients, with 75 males and 174 females, with an average age of (41.66±10.70) years. The GTAET group had a higher proportion of females 80% vs 60.3%, P<0.05 and lower BMI levels (22.86±3.11 kg/m2 vs 25.30±4.19 kg/m2 , P<0.001). There were no significant differences between the two groups in age, the prevalence of Hashimoto's thyroiditis and tumor location (P>0.05). Compared with the LACAT group, the GTAET group had longer operation time (104.63±22.29 min vs 67.88±15.69 min,P<0.001), less operation blood loss (17.65±2.83 mL vs 19.49±3.34 mL, P<0.001), and increased postoperative drainage (82.12±28.74 mL vs 68.90±21.08 mL, P= 0.01), with significant differences. There were no statistical differences in postoperative hospital stay, multifocal carcinoma rate, the number of dissected and metastatic central lymph nodes (P>0.05). In terms of postoperative complications, 20 cases of transient hypoparathyroidism occurred in the LACAT group, compared to 6 cases in the GTAET group. There was no significant difference in the incidence of transient hypoparathyroidism between the two groups (P>0.05), and no other complications were observed in the GTAET group. The GTAET group demonstrated higher satisfaction scores for incision aesthetics (P<0.05) and anterior neck sensation (P<0.05) compared to LACAT group. The incidence of postoperative dysphagia with traction sensation (6.7% vs 19.6%, P= 0.019) and anterior neck sensory abnormalities (2.3% vs 12.7%, P=0.039) was lower in the GTAET group than in the LACAT group. In subgroup comparisons within the GTAET group, T1b stage patients had more dissected lymph nodes than T1a stage patients, with significant differences (P<0.05). There were no statistical differences in other clinical characteristics among subgroups. The best-fit equation for the GTAET learning curve was y=-1.937+0.78x-0.02x²+(1.37E-4)x³, the inflection point of learning curve appeared at the 27th case.Conclusion GTAET is a safe and feasible treatment for unilateral PTC, having the advantage over the LACAT in terms of cosmetic satisfaction and anterior neck function preservation. Its operational mode integrates endoscopic and traditional surgical techniques, can reduce the difficulty of procedure, contributing to a shorter learning curve, making it worthy of clinical promotion.