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Background In the UK, non-medical prescribers (NMPs) are a significant part of the healthcare workforce. Little is known about their self-efficacy when prescribing, and their willingness to take responsibility for prescribing decisions. Objective To explore the perceptions of NMPs regarding their self-efficacy in prescribing and responsibility for prescribing decisions. Methods Cross-sectional survey of a purposive sample of NMPs on acute medical units (AMUs) across the UK. Bandura's Social Cognitive Theory informed the self-efficacy aspect of the questionnaire. Participants' views were also sought on responsibility for prescribing decisions. For quantitative data descriptive statistics were calculated. Hierarchical multiple linear regressions determined whether five independent variables improved the prediction of self-efficacy in aspects of prescribing: NMP's profession; length of time qualified as a healthcare professional and as an NMP; the number of items prescribed and hours worked per week on an AMU. Framework analysis was used to analyse the qualitative data. Results Ninety-nine valid responses were obtained. Self-efficacy overall was high. The longer the participant had been qualified as an NMP was associated with increased self-efficacy in certain aspects of prescribing. All physiotherapists, and more nurses than pharmacists were responsible for prescribing decisions. Where participants were not fully responsible, the responsibility was partial or shared. Conclusions Self-efficacy of NMPs when prescribing is influenced by several factors. The variables within this study appear to account for only a small part of this self-efficacy. Self-efficacy in prescribing appears to contribute to NMPs’ willingness to take responsibility for prescribing decisions; further influenced by their job role and the prescribing this entails. Stakeholders need to appreciate the full range of factors that influ