To investigate the effect of intermittent administration of isotretinoin capsules in patients with moderate to severe acne. Methods A total of 60 patients with moderate to severe acne admitted to the Department of Dermatology, Qingxian People's Hospital from May 2022 to May 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 30 patients in each group. The control group was treated with isotretinoin capsule for traditional daily therapy, and the observation group was treated with isotretinoin capsule for intermittent therapy. The clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate of treatment in the observation group was 90.00%, which was higher than 83.33% in the control group, but the difference was not statistically significant (P >0.05). The incidence of adverse reactions in the observation group was 3.33%, which was lower than 26.67% in the control group, and the difference was statistically significant (P <0.05). Conclusion The effect of traditional daily therapy and intermittent therapy with isotretinoin capsules is equivalent to patients with moderate to severe acne, but intermittent therapy can reduce the incidence of adverse reactions, which is worthy of clinical application.