Objective To explore the clinical feasibility of minimally invasive negative pressure aspiration in the treatment of axillary osmidrosis. Methods Sixty patients with axillary osmidrosis who were admitted to the Medical Cosmetics Department of Yantai Qishan Hospital from June 2022 to August 2023 were selected as the study objects. A random number table method was used to divide them into the reference group and the study group, with 30 patients in each group. The reference group was treated with small incision sweat adenectomy, while the study group was treated with minimally invasive negative pressure aspiration. The clinical efficacy, surgical indicators, daily activity scores and complications were compared between the two groups. Results The total effective rate of treatment in the study group was 96.67%, which was higher than 76.67% in the reference group, the difference was statistically significant (P <0.05). The operation time, postoperative fixation time, incision healing time and postoperative hospital stay in the study group were shorter than those in the reference group, the differences were statistically significant (P <0.05). The HDSS score of the study group was lower than that of the reference group, and the difference was statistically significant (P <0.05). The incidence of postoperative complications in the study group was 3.33%, which was lower than 26.67% in the reference group, the difference was statistically significant (P <0.05). Conclusion The effect of minimally invasive negative pressure aspiration in the treatment of axillary osmidrosis is better than that of small incision sweat adenectomy, which can promote rehabilitation, reduce the incidence of complications, and has high clinical application value.