Objective To investigate the clinical value on application of endoscopic parathyroiddectomy by gasless unilateral axillary approach, and perioperation management of patients. Methods Twenty-four patients with primary hyperparathyroidism were enrolled and were divided into open group (14 patients underwent open parathyroid surgery) and lumpectomy group (10 patients underwent endoscopic thyroidectomy by gasless unilateral axillary approach) according to the surgical method. All patients received the “5A” model management. The indexes related with perioperative conditions, postoperative incisional pain, and anterior cervical function were compared between the two groups. Results In the open group, 1 patient suffered from transient hoarseness after operation, 5 patients suffered from hypocalcemia on the first day after operation, and 6 patients suffered from temporary hypoparathyroidism. In the lumpectomy group, hypocalcemia occurred in 3 cases and temporary hypoparathyroidism occurred in 3 cases. There were no incision hematoma and infection cases occurred. There was no significant difference between the two groups in the incidence of hypocalcemia and the incidence of temporary hypoparathyroidism after operation (P>0.05). There was no case of incisional hematoma and infection, incisional pain, coughing and sputum excretion or painful swallowing with pain ≥3 in either group. The swallowing disorder index on postoperative day 3 and at 6 months, the scar assessment score and cosmetic satisfaction score at 6 months were higher in the open group than those in the lumpectomy group (P<0.05). Conclusion Patients underwent parathyroidectomy by gasless unilateral axillary approach have the advantages of good cosmetic results and preservation of the function of the anterior cervical region while safely removing the lesion.