IntroductionIn Belgium, oral HIV pre‐exposure prophylaxis (PrEP) is primarily provided in specialized clinical settings. Optimal implementation of PrEP services can help to substantially reduce HIV transmission. However, insights into implementation processes, and their complex interactions with local context, are limited. This study examined factors that influence providers’ adaptive responses in the implementation of PrEP services in Belgian HIV clinics.MethodsWe conducted a qualitative multiple case study on PrEP care implementation in eight HIV clinics. Thirty‐six semi‐structured interviews were conducted between January 2021 and May 2022 with a purposive sample of PrEP care providers (e.g. physicians, nurses, psychologists), supplemented by 50 hours of observations of healthcare settings and clinical interactions. Field notes from observations and verbatim interview transcripts were thematically analysed guided by a refined iteration of extended Normalisation Process Theory.ResultsImplementing PrEP care in a centralized service delivery system required considerable adaptive capacity of providers to balance the increasing workload with an adequate response to PrEP users’ individual care needs. As a result, clinic structures were re‐organized to allow for more efficient PrEP care processes, compatible with other clinic‐level priorities. Providers adapted clinical and policy norms on PrEP care (e.g. related to PrEP prescribing practices and which providers can deliver PrEP services), to flexibly tailor care to individual clients’ situations. Interprofessional relationships were reconfigured in line with organizational and clinical adaptations; these included task‐shifting from physicians to nurses, leading them to become increasingly trained and specialized in PrEP care. As nurse involvement grew, they adopted a crucial role in responding to PrEP users’ non‐medical needs (e.g. providing psychosocial support). Moreover, clinicians’ growing collaboration with sexologists and psychologists, and interactions with PrEP users’ family physician, became crucial in addressing complex psychosocial needs of PrEP clients, while also alleviating the burden of care on busy HIV clinics.ConclusionsOur study in Belgian HIV clinics reveals that the implementation of PrEP care presents a complex—multifaceted—undertaking that requires substantial adaptive work to ensure seamless integration within existing health services. To optimize integration in different settings, policies and guidelines governing PrEP care implementation should allow for sufficient flexibility and tailoring according to respective local health systems.