HIV transmission through heterosexual sex increasingly predominates, with women in sub-Saharan Africa now making up the majority of people living with HIV. In many countries gender inequalities result in further economic, social, and cultural marginalization of women These factors serve to minimize the effectiveness of male controlled HIV prevention devices, such as the condom. At least 17 microbicide candidates have reached some stage of clinical testing. Although safety and efficacy are of importance, acceptability will help determine the impact that microbicides have and shape its effectiveness as a tool in prevention. The purpose of this study was to identify factors that are associated with acceptability of vaginal microbicides among women participating in an antenatal program in Nairobi. 808 women were enrolled in the study. All of those enrolled completed the enrollment questionnaire, 589 were tested for HIV, and 536 completed the two-week questionnaire. 5.6% of women replied positively when asked whether they had ever heard of substances capable of neutralizing viruses that may be applied into the vagina before intercourse (microbicides), while 94.1% replied negatively. Prior to the HIV test, 340 women were definitely willing to take part in a study that used a microbicide to test if it protects against HIV (63.3%). After testing, 66.1% of the HIV negative women were willing, while 86.8% of the HIV positive women were definitely willing (P = .009). 68.9% of women who felt like they had been at risk of HIV infection in the past year were definitely willing to take part in a study, while 61.2% of women who did not feel like they had been at risk were willing (P = .043). These results demonstrate the importance of educating women about microbicides while also indicating that women are more likely to enroll in a microbicide trial if they feel at risk for HIV or are HIV positive. Conducting public health campaigns on microbicides, including side effects and their potential effectiveness, may help to increase awareness and ultimately enhance the accuracy of acceptability studies. This would allow women that are willing to participate in a microbicide study or use microbicides to do so in an informed way.