Objective To compare the clinical efficacy and safety of carbon dioxide (CO2) versus high-frequency electroacupuncture based on the assistance of drilling and blunt dissection in the treatment of steatocystoma multiplex.Methods A randomized,self-controlled study was performed in 15 patients.The median line of the body served as the dividing line,and the lesions on the two sides of the median line of the body were randomly divided into 2 groups to be treated with CO2 laser or high-frequency electroacupuncture,which left micropathways into the cyst cavity.After the above treatment,contents in the cysts were squeezed out or drawn out with a mosquito clamp,and the cysts were bluntly dissected.The decrustation time,erythema subsiding time,adverse reactions and recurrence were compared among lesions at different sites or with different sizes.Results For the lesions at the same sites or with similar sizes after treatment,the decrustation time and erythema subsiding time were both significantly shorter in the CO2 laser group than in the high-frequency electroacupuncture group (both P ＜ 0.05).There were significant differences in the decrustation time and erythema subsiding time among lesions at different sites or with different sizes (all P ＜ 0.05).Mild pain occurred in the 2 groups,and no hematoma or secondary infection occurred.There were significant differences in the incidence of scar formation or pigmentation between the 2 groups (both P ＜ 0.05).During the follow-up of 6-18 months,relapse occurred in 1 patient in each group.Conclusion Compared with the high-frequency electroacupuncture,CO2 laser assisted by drilling and blunt dissection shows better efficacy in the treatment of steatocystoma multiplex,and it can remove lesions at various sites at one time.