Background: O3 therapy induces moderate oxidative stress when interacting with lipids. Aim of the Work: to demonstrate the efficacy of the application of vaginal ozone insufflations in treatment of recurrent CANDIDAL vulvo-vaginitis , compared to combined vaginal and systemic antifungal agents. Patients and Methods: This randomized-controlled study was conducted on 50 women with recurrent vulvo-vaginitis, recruited from the outpatient gynecology clinic of Ain shams University Obstetrics and Gynecology Hospital, who were attending for outpatient consultation. Subjects were assigned randomly into two groups, group (A) 25 subjects, who were treated with traditional, combined, topical and systemic antifungal therapy, and (b) Group (B): 25 subjects, who were treated by vaginal ozone insufflations. Results: Twenty-two (88%) patients in the vaginal ozone group had clinical cure compared with only 14 (56%) patients in the traditional treatment group. This difference was statistically significant. Likewise, the microbiological cure rate was significantly higher in the vaginal ozone group compared with the traditional treatment group. Five out of 14 patients (35.7%) in the traditional treatment group suffered clinical recurrence compared with only 1 out of 22 patients (4.5%) in the vaginal ozone group. This difference was statistically significant. Likewise, the microbiological recurrence rate was significantly lower in the vaginal ozone group compared with the traditional treatment group. Conclusion: Ozone therapy has proven to be effective in treatment of the recurrent vulvovaginitis, where the persistence of clinical symptoms and positive culture exudates were measured.