| Objective: To explore the clinical efficacy and adverse reactions of fluconazole combined with clotrimazole suppositories in the treatment of vulvovaginal candidiasis (VVC), so as to provide reference for clinicians to choose rational drug use. Methods: A total of 102 patients with VVC diagnosed and treated in Shenyang international travel health care center from January 2017 to December 2019 were selected as the research objects. According to the random number table method, the subjects were randomly divided into two groups: the control group and the observation group (51 cases in each group). The control group was treated with clotrimazole vaginal suppository, and the observation group was treated with fluconazole and clotrimazole vaginal suppository. The clinical effect and incidence of adverse reactions were compared between the two groups. Results: The total effective rate of the observation group was 96.08%, higher than that of the control group (84.31%), P＜0.05; the incidence of adverse reactions in the observation group was 5.88%, higher than that in the control group (1.96%), but there was no significant difference between the two groups, P＞ 0.05. Conclusion: In the treatment of VVC, fluconazole combined with clotrimazole vaginal suppository is more effective and safe than single drug treatment, and it does not significantly increase the incidence of adverse reactions, which is effective and safe, and is worthy of recommendation.