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The number of gay and bisexual men (GBM) taking HIV pre-exposure prophylaxis (PrEP) to prevent HIV has rapidly increased since 2010, but limited information about barriers and facilitators to adherence has been reported outside of formal trial settings. We conducted semistructured in-depth interviews with 24 Australian cis- and transgender GBM with a history of PrEP use to gather data on adherence to PrEP. The majority of participants were able to access PrEP at no cost through implementation studies. Three key domains were explored—how individuals took PrEP, factors that aided PrEP adherence, and barriers to PrEP use. All participants recognized the importance of regular dosing to ensure protection from HIV, with some participants taking the initiative to pre-empt possible adherence obstacles and plan around these. Multiple strategies were used to aid adherence, including using tools such as a phone alarm and support and tips from other PrEP users, friends, or clinicians. Barriers to PrEP adherence included stigma, concerns about side effects, and difficulties in accessing PrEP. Although most participants encountered at least one barrier to PrEP use, they were resourceful and utilized a variety of approaches to ensure good adherence to PrEP was maintained. These narratives highlight a commitment to finding ways to make PrEP work in the daily lives of this cohort of Australian GBM, demonstrated by their active investigation of different routines to determine the most suitable dosing strategy, and creation of contingency plans if they were unable to access PrEP in their usual or preferred manner. [ABSTRACT FROM AUTHOR]