Many women continue to become infected with HIV, particularly in the Southeastern USA, despite widespread knowledge about methods to prevent its sexual transmission. This grounded theory investigation examined the decision-making process women use to guide their use or non-use of self-protective measures when engaging in sexual activity. Participants included women in the Mississippi cohort of the Women’s Interagency HIV Study who were infected with or at high risk for HIV. Theoretical sampling was used to recruit a sample of 20 primarily African American women aged between 26 and 56 years, living in rural and urban areas. Data were analysed using constant comparative method to generate a theory of the process that guided women’s self-protective decisions. Three key themes were identified: (1) sexual silence, an overall context of silence around sexuality in their communities and relationships; (2) the importance of relationships with male partners, including concepts of ‘love and trust’, ‘filling the void’ and ‘don’t rock the boat’; and (3) perceptions of risk, including ‘it never crossed my mind’, ‘it couldn’t happen to me’ and ‘assumptions about HIV’. These themes impacted on women’s understandings of HIV-related risk, making it difficult to put self-protection above other interests and diminishing their motivation to protect themselves.