Vaginal microbicides could provide an important option for women in the prevention of HIV and other STIs. Researchers have examined women's preferences for specific product characteristics; however, much remains to be learned about women's willingness to use them with a variety of partners. This study examined high-risk women's experiences using simulated microbicides during a two-week trial. Ninety-six women completed the trial by using the product and reporting their experiences with different partner types. Analyses were conducted to examine differences between women who always used the product and those who used it less than all the time and whether risk and relationship attitudes were associated with simulated microbicide use during participants' most recent sexual encounters. All participants used the product and on an average of 79-94% of sexual encounters. The majority of the participants reported liking the simulated product. Women indicated that they would want to use microbicides in order to feel in control of their health, to avoid having to ask their partner, and because microbicides would be easier to use than condoms. Women who used the product 100% of the time had less relationship power; however, greater sexual assertiveness for STI prevention predicted simulated microbicide use during the most recent sexual encounter, and interventions may need to focus on promoting sexual assertiveness for disease prevention.