BackgroundContinuing professional development (CPD) in healthcare is fundamental for making sure frontline staff practice safely and effectively. This requires practitioners to update knowledge and skills regularly to match the changing complexity of healthcare needs. The drive towards using limited resources effectively for service improvements and the need for a flexible workforce necessitate a review of ad hoc approaches to CPD.ObjectiveTo develop strategies for achieving effective CPD in healthcare.DesignA case study design drawing on principles of realist synthesis was used during two phases of the study to identify and test what works and in what circumstances.SettingOne National Health Service Trust in South East England.ParticipantsCPD stakeholders including professional regulatory bodies (n = 8), commissioners of healthcare (n = 15), facilitators of clinical skills development (n = 34), NHS staff in clinical leadership positions (n = 38), NHS staff undertaking skills development post graduate programs (n = 31), service user advocates (n = 8) and an international expert reference group (ERG) (n = 10).MethodsData sources included a review of scholarly and grey literature, an online survey and a consensus workshop. Thematic and content analyses were used during data processing.ResultsThe findings present four interdependent transformation theories comprising transforming individual practice, skills for the changing healthcare contexts, knowledge translation and workplace cultures to optimize learning, development and healthcare performance.ConclusionsThe transformation theories contextualize CPD drivers and identify conditions conducive for effective CPD. Practitioner driven CPD in healthcare is effective within supportive organizations, facilitated workplace learning and effective workplace cultures. Organizations and teams with shared values and purpose enable active generation of knowledge from practice and the use of different types of knowledge for service improvements.