Objective To explore the clinical efficacy of isotretinoin combined with red and blue light in the treatment of patients with moderate to severe acne. Methods A total of 80 patients with moderate to severe acne admitted to our hospital from August 2019 to August 2021 were selected as the research objects. They were divided into control group and study group by random number table method, with 40 patients in each group. The control group was treated with isotretinoin, and the study group was treated with isotretinoin combined with red and blue light. The ECCA score, remission degree of skin lesions and clinical efficacy were compared between the two groups. Results The ECCA score of the study group was lower than that of the control group after treatment, and the difference was statistically significant (P<0.05). The skin lesions of the two groups after treatment were better than those before treatment, and the study group was better than the control group, the difference was statistically significant (P<0.05). The total effective rate of treatment in the study group was higher than that in the control group, the difference was statistically significant (P<0.05). Conclusion Isotretinoin combined with red and blue light can improve the ECCA score of patients with moderate to severe acne, effectively alleviate the skin lesions of patients, and improve the clinical efficacy, which is worthy of application.