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Background and Aims: Long‐acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder that is generating positive outcomes. Negative effects are typically mild and transient, but can occasionally be serious, resulting in treatment discontinuation/non‐adherence. This paper aims to analyse patients' accounts of how they felt during the first 72 h after initiating LAIB. Methods: Semi‐structured interviews were conducted (June 2021–March 2022) with 26 people (18 males and 8 females) who had started LAIB within the previous 72 h. Participants were recruited from treatment services in England and Wales and were interviewed by telephone using a topic guide. Interviews were audio‐recorded, transcribed and coded. The concepts of embodiment and embodied cognition framed the analyses. Data on participants' substance use, initiation onto LAIB and feelings were tabulated. Next, participants' accounts of how they felt were analysed following the stages of Iterative Categorization. Results: Participants reported complex combinations of changing negative and positive feelings. Bodily experiences included withdrawal symptoms, poor sleep, injection‐site pain/soreness, lethargy and heightened senses inducing nausea ('distressed bodies'), but also enhanced somatic wellbeing, improved sleep, better skin, increased appetite, reduced constipation and heightened senses inducing pleasure ('returning body functions'). Cognitive responses included anxiety, uncertainties and low mood/depression ('the mind in crisis') and improved mood, greater positivity and reduced craving ('feeling psychologically better'). Whereas most negative effects reported are widely recognized, the early benefits of treatment described are less well‐documented and may be an overlooked distinctive feature of LAIB. Conclusions: During the first 72 h after initiating long‐acting injectable buprenorphine, new patients report experiencing a range of interconnected positive and negative short‐term effects. Providing new patients with information about the range and nature of these effects can prepare them for what to expect and help them manage feelings and reduce anxiety. In turn, this may increase medication adherence. [ABSTRACT FROM AUTHOR]