This review synthesises qualitative research on pre-exposure prophylaxis (PrEP) uptake by sexual minority men to provide an overarching conceptualisation of the implementation processes involved. Twenty-four studies—comprising 734 participants from USA, UK, France, Canada, and Taiwan—were synthesised using thematic synthesis. The synthesis elucidates the dual significance of PrEP uptake: (1) risk management: reinforcing relational circumstances, and rebalancing safety and risk; and (2) sexual empowerment: reclaiming health and sexuality and refocusing on sexual fulfillment and intimacy. Overall, the findings show how gay and bisexual men use PrEP to reconcile their antagonistic desires for intimacy and safety by recalibrating protection and reimagining intimacy. This review conceptualises the essence of users’ experiences of PrEP implementation as reconciliation work—the labour and agency in making and remaking practices to manage discontinuities and incongruities—about the new HIV prevention modality. The concept of reconciliation work illustrates how using PrEP influences users’ practices, which in turn, shape the meanings of PrEP use within the community. This work engenders contingent transformations and outcomes beyond HIV protection, encompassing the broader aspects of health and sexuality. Findings support the adoption of more holistic and empowering approaches to sexual health promotion and intervention.