Objective To explore the effect of clarithromycin tablets combined with fusidic acid cream in the treatment of acne vulgaris. Methods From May 2022 to May 2023, 60 patients with acne vulgaris admitted to Fushui Town Public Central Health Centre of Shangnan County were selected as observation objects. According to different treatment methods, they were divided into control group and observation group, with 30 patients in each group. The control group was treated with clarithromycin tablets, and the observation group was treated with clarithromycin tablets combined with fusidic acid cream. The clinical efficacy, acne grading, adverse reactions and quality of life were compared between the two groups. Results The total effective rate of treatment in the observation group was 96.67%, which was higher than 80.00% in the control group (P <0.05). The proportion of grade Ⅰ and grade Ⅱ acne in the observation group was higher than that in the control group, and the proportion of grade Ⅲ and grade Ⅳ acne was lower than that in the control group (P <0.05). The incidence of adverse reactions in the observation group was lower than that in the control group (P <0.05). The scores of all dimensions of quality of life in the observation group were higher than those in the control group (P <0.05). Conclusion Clarithromycin tablets combined with fusidic acid cream has a good effect in the treatment of acne vulgaris, which can not only alleviate the symptoms of acne, but also reduce the incidence of adverse reactions, promote the recovery of skin appearance as soon as possible, so as to improve the negative emotions of patients with negative inferiority and improve their quality of life.