Objects of risk mitigation are typically viewed as neutral items that limit exposure to an established hazard. However, people may refuse to adopt such tools, even when they feel vulnerable. This article explores how people assess their personal risk and mitigation options by examining PrEP use for HIV prevention. Drawing on semi-structured in-depth interviews with 40 Black and Latino gay, bisexual, and queer men, I argue PrEP uptake is a socially contextualized decision influenced by relational concerns. I develop the concept of relational inoculation, wherein individuals enact a sense of protection against harm through relational work. As individuals consider PrEP, they also contemplate how it may bolster or undermine intimacy they value for reducing interpersonal HIV exposure, as well as dispelling stigmatized notions of riskiness held by their intersecting ethno-racial and sexual minority communities. I develop testable propositions about how respondents’ HIV risk assessments and PrEP use are enmeshed in a societal context of surveillance, in ongoing relations with intimate partners and socially significant others, and in navigation of community belonging within this milieu of risk. This article contributes to sociological research at the nexus of race, sexuality, and health, and offers health policy insight.