Pre-exposure prophylaxis (PrEP) is an effective tool for reducing HIV infection, primarily targeting men who have sex with men (MSM) and transgender individuals who are most at risk. However, despite awareness of this preventive treatment and a positive perception of its effectiveness, only a minority of eligible individuals are using it. To better understand this situation, we sought to examine the factors that predict belonging to the group of respondents who use PrEP as well as to a group of non-PrEP users—who met eligibility criteria at the time of the survey and reported a positive view of the treatment’s effectiveness—among participants in the 2018 Net Gay Barometer. This edition included 10,853 respondents, of whom 3,251 (38.7%) met the eligibility criteria for PrEP in France in 2018. Among them, the 445 PrEP users and 1,327 non-PrEP users with a positive view of PrEP’s effectiveness were compared to the 1,479 non-PrEP users—who were less informed or skeptical—who constituted the reference group in the multinomial logistic regression analysis. Although similar in many respects to other eligible participants, PrEP users are more likely to engage in unprotected anal sex in serodiscordant relationships and in chemsex, even though these risky behaviors are a significant concern for them. Non-PrEP users with a positive perception of the treatment share similarities with them in terms of sexual practices, proximity to the Paris region, greater knowledge of harm reduction strategies, and a sense of belonging to the LGBTQI (lesbian, gay, bisexual, trans, queer, intersex) community. Respondents in the reference group, who are more often bisexual, have less knowledge of behavioral risk reduction strategies, while being more likely to report regularly not using condoms during anal sex, without this being a concern for them. Since PrEP is free in France and made available for initial prescription by general practitioners, efforts should be made to promote this prevention tool among a population that identifies less strongly with and is more distant from the LGBTQI community, while maintaining a holistic approach to sexual health.