Background This article describes perceptions and experiences related to the preexposure prophylaxis (PrEP) care continuum of Mexican men who have sex with men (MSM) and transwomen (TW). Methods Between June and July 2020, we applied 24 online semistructured interviews regarding PrEP use with 10 PrEP users, 6 ex-users, and 8 potential users (at risk, not enrolled). Results Awareness: TW did not always receive the information they needed from trusted people. Acceptability: Potential users were reluctant to use PrEP because of fear of adverse effects, and only a few participants worried about stigma. Uptake: Potential users missed their enrollment visit and did not know how to reschedule. Adherence: Barriers included routine changes interfering with PrEP-taking habits (arriving home later, traveling, etc.), whereas feeling protected was reported as a facilitator. Retention: Ex-users quit PrEP services, mostly without reducing their HIV risk, because of difficulties keeping appointments and fearing long-term effects. Conclusion Inclusive awareness activities, tackling misbeliefs regarding adverse effects, and more flexible services may improve PrEP usage and enhance its impact.