Introduction: The aim of the study was to compare the feasibility and safety of endoscopic thyroid lobectomy via axillary-breast-shoulder approach (ET via ABS) with a conventional open thyroid lobectomy (OT). Methods: From November 2014 to December 2015, 20 patients with unilateral benign thyroid nodules were treated with ET via ABS and another 20 patients were treated with an OT. We analyzed the clinical characteristics postoperative complications, pain, and patient satisfaction. Results: No statistically significant differences occurred between groups except the mean ages of the OT group and the ET via ABS group were 55 and 44 years, respectively (p = 0.015). The mean operative time was almost the same in both groups (116 min in the OT group and 114 min in the ET via ABS group). Blood loss was significantly higher in the OT group than in the ET via ABS group (p = 0.042) but postoperative drainage was detected more in the ET via ABS group (p < 0.001). Early postoperative pain was significantly less in the ET via ABS group (p = 0.026). The hospital stay was three days in OT group and four days in ET via ABS group (p = 0.909). Postoperative complications such as hematoma, hoarseness, dysphagia, and prolonged subcutaneous emphysema were detected only in the ET via ABS group but without statistical difference. More patients were "very satisfied" with the treatment in the ET via ABS group than in the OT group. Conclusion: The ET via ABS is as safe and effective as the OT for patients with unilateral thyroid nodules. With less early postoperative pain and higher patient satisfaction, this endoscopic thyroidectomy approach should be considered in patients who concern about cosmetic results.