Background: UK general practitioners (GPs) are leaving direct patient care in significant numbers. We undertook a systematic review of qualitative research to identify factors affecting GPs' leaving behaviour in the workforce as part of a wider mixed methods study (ReGROUP)., Objective: To identify factors that affect GPs' decisions to leave direct patient care., Methods: Qualitative interview-based studies were identified and their quality was assessed. A thematic analysis was performed and an explanatory model was constructed providing an overview of factors affecting UK GPs. Non-UK studies were considered separately., Results: Six UK interview-based studies and one Australian interview-based study were identified. Three central dynamics that are key to understanding UK GP leaving behaviour were identified: factors associated with low job satisfaction, high job satisfaction and those linked to the doctor-patient relationship. The importance of contextual influence on job satisfaction emerged. GPs with high job satisfaction described feeling supported by good practice relationships, while GPs with poor job satisfaction described feeling overworked and unsupported with negatively impacted doctor-patient relationships., Conclusions: Many GPs report that job satisfaction directly relates to the quality of the doctor-patient relationship. Combined with changing relationships with patients and interfaces with secondary care, and the gradual sense of loss of autonomy within the workplace, many GPs report a reduction in job satisfaction. Once job satisfaction has become negatively impacted, the combined pressure of increased patient demand and workload, together with other stress factors, has left many feeling unsupported and vulnerable to burn-out and ill health, and ultimately to the decision to leave general practice., Competing Interests: Competing interests: None, except that two of the included studies were conducted by two of the coauthors of this systematic review (JLC and AS) and the principal investigator of the wider ReGROUP study of which this systematic review is a part (JLC). Neither AS or JLC had any involvement in the detailed data extraction or quality assessment of their studies or any of the other studies. Also, AA has received personal fees from the Northern, Eastern and Western Devon CCG, Devon Local Medical Committee, British Medical Association, University of Exeter, CLAHRC South West Peninsula, and NHS England Medical Directorate (South), outside of this work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)