Maintaining routines of medication dosing requires effort amidst the variabilities of everyday life. This article offers a sociomaterial analysis of how the oral HIV prevention regimen, pre‐exposure prophylaxis (PrEP), is put to use and made to work, including in situations which disrupt or complicate dosing regimes. Other than a daily pill, PrEP can be taken less frequently based on anticipated sexual activity and HIV risk, including ‘on‐demand’ and ‘periodic’ dosing. Drawing on 40 interviews with PrEP users in Australia in 2022, we explore PrEP and its dosing as features of assemblages in which bodies, routines, desires, material objects and the home environment interact. Dosing emerges as a practice of coordination involving dosette boxes, blister packs, alarms, partners, pets, planning sex, routines and domestic space, and as an effect of experimentations with timing to suit life circumstances and manage side effects. Dosing is materialised in the mundane; a practice that is made to work, as well as domesticated, in its situations. Although there are no ‘simple’ solutions to adherence, our analysis offers practical insights into how routine, planning and experimentation come together to capacitate PrEP to work in people’s lives, in sometimes unexpected ways, including through adaptations of PrEP dosing.