Background: Vulvovaginal candidiasis is one of the most common infections in gynecologic filed, and non–albicans Candida species are emerging causative microorganisms. This species shows resistance to routine treatments. One of the suggested treatments is administration of vaginal suppositories of boric acid. The aim of the present study was to compare boric acid with clotrimazole in the treatment of recurrent or resistant vulvovaginitis. Methods: In a double-blind, randomized clinical trial, 90 non-pregnant women were enrolled. The patients were divided into two groups to receive; boric acid (300 mg twice a day for 2 weeks) or clotrimazole (100 mg once a day for 2 weeks) intra-vaginally. Treatment responses were monitored by laboratory and clinical data. Results: Treatment responses were significantly different in laboratory results for boric acid and clotrimazole groups (86.7% v 60%, P= 0.004). Clinical responses (improved signs and symptoms) showed no significant differences (8.2. v 6.5, P= 0.02). Drug side effects were not different in boric acid and clotrimazole groups (13.3% v 11.1%, P= 0.75). Conclusion: Intra-vaginal administration of boric acid is more effective than clotrimazole in vaginal candidiasis caused by non-albicans species.