〔Abstract〕 Objective To evaluate whether a compound colloidal sulfur emulsion is as effective as peroxybenzoyl gel in treating acne vulgaris. Methods A total of 120 patients with acne vulgaris were recruited from the dermatology clinic of Shenzhen Luohu Hospital of Traditional Chinese Medicine from August 1, 2022 to November 20, 2022, and were randomly divided into a control group (5% oxybenzoyl gel, 59 cases) and an observation group (61 cases). Patients in both groups were treated continuously for 28 days, and were followed up at 1, 2, 3 and 4 weeks after medication. The therapeutic effect, the changes in the number and area of skin lesions, and the degree of subjective feeling to drug stimulation were compared between the two groups. Results After 4 weeks of treatment, the difference in response rate between the two groups was 1.07%, 95% CI was (-3.38, 5.24), and the lower 95% CI of the difference was (3.38%) > the non-inferiority threshold was (5%). In addition to 2 weeks of follow-up, the skin area of the control group was significantly smaller than that of the observation group, the difference was statistically significant (P < 0.05), and there was no statistically significant difference in the number and area of skin lesions between the two groups in other weeks (P > 0.05). At different follow-up times, there were statistically significant differences between the two groups in the degree of sensory stimulation of the drugs used (P < 0.001). Conclusion In the treatment of acne vulgaris inflammatory papules, the therapeutic effect of compound colloidal sulfur emulsion is not inferior to that of peroxybenzoyl gel, and it is less irritating.