To investigate the efficacy, safety and advantages of gasless unilateral axillary approach (GUAA) in endoscopic thyroid surgery. A total of 334 patients who underwent the GUAA endoscopic thyroid surgery (GUAA group) or conventional open thyroid surgery (OS group) in the Department of Head and Neck Surgery of Zhejiang Cancer Hospital from January 2017 to June 2018 were retrospectively analyzed. There were 45 males and 289 females, aged from 12 to 72 years old, of whom 139 patients were assigned to GUAA group and 195 patients to OS group. Pathological results included papillary thyroid carcinoma (282 cases), nodular goiter (41 cases) and thyroid adenoma (11 cases). Surgical exploration development curve of GUAA group was drawn and was divided into two parts: the technical exploration stage and the technical stable stage. Surgical efficiency, incidences of complications, and incision satisfaction were compared between GUAA group in technical stable stage and OS group. SPSS 25.0 software was adopted for statistical analysis. The mean age in GUAA group was younger than that in OS group, with a significant difference [(35.3±9.5) years (48.1±10.6) years, =11.31, <0.01]. The cases in the endoscope group were divided into technical exploration stage for 51 cases and technical stable stage for 88 cases according to the exploration and development curve. In unilateral radical thyroidectomy and unilateral thyroid lobectomy, the mean operation time [(90.6±18.6) min and (93.5±22.0) min] and postoperative drainage volumes [(121.5±87.6) ml and (155.5±69.1) ml] of GUAA group in the stable stage were more than those of OS group [(61.6±15.6) min and (46.5±8.4) min] and [(93.2±42.3) ml and (78.9±48.7) ml]. The difference was statistically significant (=12.28, 7.23, 3.35 and 3.05 respectively, all 0.05 and (16.3±14.1) ml (11.9±5.1) ml, =1.05, >0.05]. Compared with OS group, GUAA group had the lower incidence of anterior cervical discomfort during swallowing (2.3% 29.2%, <0.01) and the higher incision satisfaction score (1.1±0.5 2.8±0.7, =21.12, <0.01), however, GUAA group had the higher incidence of supraclavicular (or infraclavicular) numbness after surgery (5.7% 0, 0.05). GUAA endoscopic thyroid surgery is a safe method with high cosmetic satisfaction.