Assess efficacy of intermittent intravaginal metronidazole gel treatment in reducing frequency of bacterial vaginosis (BV). Randomized, double-masked, placebo-controlled phase 3 trial. Postnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in Blantyre, Malawi. Nonpregnant HIV-uninfected and -infected women. Intravaginal metronidazole treatment and placebo gels provided at baseline and every 3 mo for 1 y. PRIMARY: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1 mo after product dispensation (post-treatment evaluation PTE), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence. BASELINE: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women. At the PTEs the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of intravaginal metronidazole treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83-0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89-1.01 in HIV-infected women. Intravaginal metronidazole treatment gel significantly increased BV clearance (adjusted hazard ratio HR 1.34, 95% CI 1.07-1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06-1.58 among HIV-infected women) but was not associated with decreased BV recurrence. No serious adverse events were related to use of intravaginal gels. Intermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.