Objective. To evaluate the clinical and laboratory efficiency of two-step therapy with Depantol and Femilex for acute nonspecific and mixed vaginitis. Subjects and methods. The prospective observational study enrolled 200 patients aged 18-45 years with acute nonspecific and mixed (bacterial-fungal) vaginitis, who were stratified according to the diagnosis and the presence of pregnancy. All the patients underwent pH measurements over time and microscopic and molecular biological studies of vaginal discharge using the femoflor test, by evaluating microbiocenosis. Vaginitis therapy included Depantol as 1 vaginal suppository twice daily for 7 days, then Femilex as 1 vaginal suppository daily for 10 days. Descriptive statistical methods; one-way analysis of variance; a test for difference in proportions and means; Student’s t-test; a chi-square (χ2 ) test; and a paired Wilcoxon test were used in the analysis. The differences were considered significant at p <0.05. Results. Depantol and Femilex used for two-step therapy for acute nonspecific and mixed vaginitis achieved a clinical and laboratory efficiency of 91% and there were no significant differences between non-pregnant and pregnant women. The recurrence rate for vaginitis after two-month follow-up is determined by accompanying risk factors and does not exceed 3%. Conclusion. The sequential use of Depantol vaginal suppositories for 7 days and Femilex vaginal suppositories for 10 days is an effective two-step treatment regimen for acute nonspecific and mixed (bacterial-fungal) vaginitis in reproductive-aged women, which allows restoration of normocenosis in more than 90% of patients. © 2019, Bionika Media Ltd.. All rights reserved.