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Aim: In this study, we tested the efficacy, safety, and tolerability of vaginal ovules and a vaginal douche containing tyndallized ferments in women affected by nonspecific vulvovaginitis, with or without the human papillomavirus (HPV)., Methods: The study included 91 female patients and had a randomized, controlled sequential design, with parallel groups. Ovules and douche were tested and compared to a control group treated with sterile physiological solution. Total symptom score (TSS), individual signs and symptoms, therapeutic success were evaluated, as well as safety and tolerability., Results: The tyndallized ferments formulations (ovules and douche) had a safe and tolerable profile, and resulted in a significant decrease in TSS in patients affected by nonspecific vulvovaginitis, both at 5 and 10 days of treatment, when compared to a control group. The treatment was more effective than the control in reducing symptoms such as vulvar erythema, vulvar edema, itching, and burning. Patients affected by vulvovaginitis and HPV-positive received a 30 days treatment either with ovules or ovules + douche, and we observed an improvement at Day 30 compared to Day 0, for both regimens., Conclusions: Our study suggests that topical treatment with tyndallized ferments is a safe and effective strategy to reduce symptoms of nonspecific vulvovaginitis., (© 2024 Japan Society of Obstetrics and Gynecology.)