Background: Bacterial vaginosis (BV) is a common polymicrobial disease associated with numerous negative reproductive health outcomes, including an increased risk of human immunodeficiency virus acquisition. BV is treatable with antibiotics, but relapse is common. A more detailed understanding of bacterial dynamics during antibiotic therapy for BV could identify conditions that favor establishment, maintenance, and eradication of BV-associated bacterial species, thereby improving treatment outcomes. Methods: We used mathematical models to analyze daily quantitative measurements of 11 key bacterial species during metronidazole treatment for 15 cases of BV. Results: We identified complete reorganization of vaginal bacterial composition within a day of initiating therapy. Although baseline bacterial levels predicted a longer time to clearance, all anaerobic species were eliminated rapidly within a median of 3 days. However, reemergence of BV-associated species was common following treatment cessation. Gardnerella vaginalis, a facultative anaerobe, was cleared more slowly than anaerobic BV-associated species, and levels of G. vaginalis often rebounded during treatment.We observed gradual Lactobacillus species growth, indicating that untargeted microbes fill the transient vacuum formed during treatment. Conclusions: Under antibiotic pressure, the human microbiome can undergo rapid shifts on a scale of hours. When treatment is stopped, BV-associated bacteria quickly reemerge, suggesting a possible role for intermittent prophylactic treatment.