New medicines can transform routines and priorities in clinical practice, but how do clinicians think and feel about these changes, and how does it affect their work? In Australia, the HIV prevention regimen pre-exposure prophylaxis (PrEP) has been rapidly rolled out, transforming the sexual cultures and practices of users, but less attention has been given to the ways PrEP has reconfigured clinical practice. This paper draws on 28 qualitative semi-structured interviews conducted between 2019 and 2020 with PrEP-providing doctors and nurses in Australia to consider how they have affectively engaged with PrEP and put it into practice. Through a reflexive thematic analysis, we explore how clinicians adapted to PrEP, how the field of HIV prevention has been transformed, and how these developments have changed how clinicians approach patients. While the introduction of PrEP was initially received with uncertainty and shock, clinicians described PrEP as enjoyable to prescribe, and better aligned with the moral duties of sexual health consultations than existing HIV prevention strategies like condoms. Through approaching clinical work as an ‘affective practice’, we argue for attending not only to how new interventions change expectations and practices, but also how these changes are felt and valued by clinicians.