Pre-exposure prophylaxis (PrEP) is an effective yet under-utilised method for preventing HIV transmission in high-risk groups. Despite ongoing social marketing to increase PrEP awareness, few studies have evaluated public responses. This paper contextualises negative responses to Chicago's PrEP4Love campaign. In February 2016, a sex-positive ad campaign called PrEP4Love was launched online and throughout public spaces in Chicago. A gender and sexuality inclusive campaign, PrEP4Love is intended to be culturally responsive and sex positive, while retaining a focus on risk reduction. Advertisements prominently feature Black sexual minority men, and Black transgender women, and were strategically placed in diverse Chicago neighbourhoods. In response, there were 212 new callers to the PrEPLine during the two-month study period. Negative responses were concerned with: negatively depicting Black homosexuality (4), general anti-LGBTQ comments (7), adverse effects on children (6), sexually explicit nature (5), and general stigmatisation of racial minorities (4). Discussion focuses on sex-positive frameworks, normalising intimacy, stigma and historical mistrust of medical and pharmaceutical institutions, and the social meanings of biomedical prevention technologies (e.g. PrEP) in relation to dominant norms of sexuality and gender. This study is the first to investigate public responses to a sex-positive PrEP campaign. More studies of PrEP social marketing are needed to evaluate targeted public health campaigns to guide future PrEP promotion strategies.