Objective To analyze the efficacy and safety of oral isotretinoin combined with radiofrequency therapy in patients with moderate to severe acne. Methods A total of 58 patients with moderate to severe acne admitted to People's Hospital of Yangzhong City from January 2025 to May 2025 were selected, and they were divided into group A and group B according to different treatment methods, with 29 patients in each group. Group A was treated with oral isotretinoin, and group B was treated with oral isotretinoin combined with radiofrequency therapy. The acne severity, clinical efficacy, adverse reaction rate, quality of life and recurrence rate were compared between the two groups. Results After 1, 2 and 6 weeks of treatment, the GAGS scores of the two groups were lower than those before treatment, and those of group B were lower than those of group A (P <0.05). The total effective rate of group B (96.55%) was higher than that of group A (75.86%) (P <0.05). The incidence of adverse reactions in group B (3.45%) was lower than that in group A (24.14%) (P <0.05). The scores of each item of DLQI in the two groups after treatment were lower than those before treatment, and those in group B were lower than those in group A (P <0.05). The recurrence rate of group B (3.45%) was lower than that of group A (24.14%) (P <0.05). Conclusion Oral isotretinoin combined with radiofrequency therapy has a good effect in patients with moderate to severe acne. It can not only effectively reduce the severity of acne, but also lower the risk of adverse reactions and recurrence, which is beneficial to improving patients' quality of life, with good efficacy and safety .