HIV pre-exposure prophylaxis (PrEP) is a highly effective prevention strategy, yet awareness, knowledge, and willingness to use it among people who inject drugs (PWID) remains inadequate despite widespread eligibility. Stigma, particularly HIV-stigmatizing beliefs and attitudes, may be a key barrier to engagement at early stages of the PrEP care continuum. We examine how HIV-stigmatizing beliefs and attitudes affect PrEP awareness, knowledge, and willingness among PWID. We surveyed 262 HIV-negative PWID in Los Angeles and Denver (2021–2023) and used structural equation modeling to examine associations between HIV-stigmatizing beliefs and attitudes (11-item validated scale with α = 0.899 and 1-factor structure) and three early PrEP outcomes: awareness, knowledge, and willingness, while controlling for race/ethnicity, gender, housing status, and conducted sub-analyses on willingness to use long-acting injectable PrEP. HIV-stigmatizing beliefs and attitudes were significantly associated with lower PrEP awareness (β − 0.212, p < 0.001) and less accurate knowledge (β − 0.179, p = 0.006). Accurate knowledge was associated with greater willingness to use PrEP (β 0.175, p = 0.027). Black, Indigenous, and Other Persons of Color (BIPOC) participants reported higher HIV-stigmatizing beliefs and attitudes than non-Hispanic White participants (β 0.196, p = 0.003). Over half (56
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