Background Bacterial vaginosis (BV) treatment failures and recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. Methods Women with BV (Bronx, NY and Thika, Kenya) received 7 days of oral metronidazole at enrollment (Day 0) and underwent genital tract sampling of microbiome (16S rRNA gene sequencing), transcriptome (RNAseq), and immune mediator concentrations on Day 0, 15 and 35. Results Bronx participants were more likely than Thika participants to clinically respond to metronidazole (19/20 vs 10/18, respectively, p=0.0067) and by changes in microbiota composition and diversity. After dichotomizing the cohort into responders and non-responders by change in alpha diversity between Day 35 and Day 0, we identified transcription differences associated with chemokine signaling (q=0.002) and immune system process (q=2.5e-8) that differentiated responders from non-responders were present at enrollment. Responders had significantly lower levels of CXCL9 in cervicovaginal lavage on Day 0 (p< 0.007) and concentrations of CXCL9, CXCL10 and MCP-1 increased significantly between Day 0 and Day 35 in responders versus non-responders. Conclusions Response to metronidazole is characterized by significant changes in chemokines and related transcripts suggesting that treatments that promote these pathways may prove beneficial.