Objective To explore the effect of modified Xiaocuo prescription combined with red and blue light irradiation in the treatment of moderate to severe acne vulgaris. Methods A total of 80 patients with moderate to severe acne vulgaris admitted to the Department of Dermatology of Huanghua Municipal People's Hospital from August 2020 to July 2022 were selected as the research objects. They were divided into control group (n=40) and observation group (n=40) by random number table method. The control group was treated with red and blue light irradiation, and the observation group was treated with modified Xiaocuo prescription with red and blue light irradiation. The clinical efficacy, TCM syndrome score, skin lesion score, pain status, incidence of adverse reactions and recurrence rate were compared between the two groups. Results The total effective rate of the observation group was 97.50%, which was higher than 80.00% of the control group (P<0.05), and the difference was statistically significant. After treatment, the scores of TCM syndromes, skin lesions and pain in the observation group were lower than those in the control group, and the difference was statistically significant (P<0.05). The incidence of adverse reactions in the observation group was 5.00%, which was lower than 22.50% in the control group, and the difference was statistically significant (P<0.05). The recurrence rate of the observation group was slightly lower than that of the control group, but the difference was not statistically significant (P>0.05). Conclusion Modified Xiaocuo prescription combined with red and blue light irradiation is effective in the treatment of moderate to severe acne vulgaris. It is beneficial to promote the recovery of skin lesions, reduce pain, and has high safety