In sub-Saharan Africa, HIV incidence andprevalence remain disproportionately high among women.Vaginal rings (VRs) have been formulated for the deliveryof antiretroviral-based microbicides, and their favorablesafety and tolerability profiles reported in clinical studies.Although the concept of drug release through a VR hasexisted since 1970, and VRs have been marketed since1992 for contraceptive or hormone replacement purposes,VR use as a microbicide delivery system is a novelapplication. This is the first study to evaluate VR adherenceamong African women in the context of its potential use asan HIV prevention method, to examine predictors ofadherence, and to describe clinical or contextual reasonsfor VR removals or nonadherence. This was a randomizedtrial of the safety and acceptability of a placebo VR wornfor 12 weeks in 170 HIV-negative, African women aged18–35 in four clinic sites in South Africa and Tanzania.The findings suggest that adherence to VR use in thecontext of HIV prevention trials in these communitiesshould be high, thereby enabling more accurate assessmentof an active microbicide safety and efficacy.Keywords Vaginal ring ? Adherence ? Sub-SaharanAfrica ? Female-controlled HIV prevention methods ?Microbicide delivery