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Microbicides are an emerging HIV-focused biomedical intervention offering protection against HIV. Despite potential benefits, willingness to use these products has not been well studied, especially among females who use unregulated drugs. Between June 2021 and May 2022, data were drawn from two prospective cohorts of people who use drugs in Vancouver, Canada. Analyses focused on participants who were female sex at birth and sexually active. Findings indicate low awareness and willingness to use microbicides among females who use drugs in Vancouver, Canada. While microbicides appear to offer important opportunities as a biomedical intervention, initial low levels of reported willingness indicate the impact may be limited.