Pleasure-seeking plays a role in prevention (means choices and use), and in the sexual quality of life of men who have sex with men (MSM). Since HIV is a major threat to MSM health, new means of prevention, like pre-exposure prophylaxis (PrEP), must meet the needs of MSM to be fully efficient. Using a psychosocial approach, we examined how pleasure-seeking plays a role in participation of MSM in “ANRS-IPERGAY,” a community-based trial on sexual health which included sexual on-demand PrEP. Thirteen semistructured collective interviews were conducted with 45 participants. First, we analyzed participants’ search for new prevention means due to previous failures in condom use. We found that participants perceived condoms as a barrier—both materially and symbolically—to pleasure and desire, causing anxiety and stress considering sexual intercourse. Second, we explored representations and attitudes concerning pleasure within the context of PrEP. We found that PrEP allowed participants to freely choose their desired sexual positions and to better enjoy intimacy. Third, we studied the sexual quality of life for PrEP users in ANRS-IPERGAY and found an improvement. Thanks to the community-based design of the trial, this new prevention tool became a means to develop agency and empowerment for participants, not only in negotiating individual prevention but also in opposing the normative and stigmatizing discourse on sexuality and HIV. In conclusion, pleasure-seeking appears to be an essential element of sexual fulfillment that needs to be integrated as a positive notion in the study of HIV prevention.