Context: Infectious vaginitis, often worsening quality of life, is a frequent cause of consultation. Its various etiologies (fungal, bacterial or mixed), difficulties in clinical diagnosis as well as limits of microbiological analysis can justify the choice of a broad spectrum first-line treatment. The vaginal soft capsule with a Nystatin-Neomycin-Polymyxin B combination has a large experience of a well-established use in infectious vaginitis. Objective: To update efficacy and safety data of the NNP combination and its relevance as first line empirical treatment. Methods: Analysis of two recently conducted studies evaluating the efficacy of NNP combination in vaginal infections: a prospective open multicenter study and an international, randomized, double-blind, comparative vs miconazole study. Patients: 169 patients with symptoms of infectious vaginitis were included in the first study and 658 patients in the second. Interventions: All patients received 12 days treatment with the NNP combination in both studies with additionally Miconazole treatment for 3 days followed by placebo for 9 days in the comparative group of the second study. Main Outcome Measure: Success or failure of treatment was assessed by clinical examination. Results: In the first study, clinical success was 97.8% and microbiological cure was 81.3%. Tolerance and compliance were also good. In the second study, the risk of therapeutic failure rate was reduced by 36% for patients treated with the NNP over Miconazole irrespective of the etiology. The success rate was higher in the NNP group with 91.1% vs 86.7% in the Miconazole group close to the statistically significant level. Vaginal burning was lower in the NNP group than in Miconazole group at day 2 of the treatment. As for tolerance, the incidence of ADRs relatively to AEs was significantly higher in the Miconazole group. The treatment compliance was very good with better patients and investigators satisfaction in the NNP group. Conclusions: Due to the diversity of etiologies of infectious vaginitis and the lack of precision in clinical and microbiological diagnosis, first-line empirical treatment with large spectrum is indicated. The results of the studies with NNP show its clinical and microbiological efficacy in this indication with a quick relief of patient symptoms.