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Introduction: Non-medical prescribing has the potential to deliver innovative healthcare within limited finances. However, uptake has been slow, and a proportion of non-medical prescribers do not use the qualification. This systematic review aimed to describe the facilitators and barriers to non-medical prescribing in the United Kingdom. Methods: The systematic review and thematic analysis included qualitative and mixed methods papers reporting facilitators and barriers to independent non-medical prescribing in the United Kingdom. The following databases were searched to identify relevant papers: AMED, ASSIA, BNI, CINAHL, EMBASE, ERIC, MEDLINE, Open Grey, Open access theses and dissertations, and Web of Science. Papers published between 2006 and March 2017 were included. Studies were quality assessed using a validated tool (QATSDD), then underwent thematic analysis. The protocol was registered with PROSPERO (CRD42015019786). Results: Of 3991 potentially relevant identified studies, 42 were eligible for inclusion. The studies were generally of moderate quality (83%), and most (71%) were published 2007–2012. The nursing profession dominated the studies (30/42). Thematic analysis identified three overarching themes: non-medical prescriber, human factors, and organisational aspects. Each theme consisted of several sub-themes; the four most highly mentioned were ‘medical professionals’, ‘area of competence’, ‘impact on time’ and ‘service’. Sub-themes were frequently interdependent on each other, having the potential to act as a barrier or facilitator depending on circumstances. Discussion: Addressing the identified themes and subthemes enables strategies to be developed to support and optimise non-medical prescribing. Further research is required to identify if similar themes are encountered by other non-medical prescribing groups than nurses and pharmacists. [ABSTRACT FROM AUTHOR]