Abstract Objectives There is widespread use of unlicensed medicines within primary and secondary care but little information is available around how these medicines are used. This analysis examines and evaluates the content and quality of relevant guidance documentation currently in use within the UK. Methods Guidance documents were identified through a literature search as well as email requests to pharmacy organisations throughout the UK. Unlicensed medicine documentation suitable for inclusion in the analysis underwent thematic analysis and quality assessment using the AGREE II tool. Key findings Thematic analysis of 52 guidelines revealed four parent themes: (1) Professional responsibility (2) Usage practicalities (3) Risk versus benefit (4) Controlling use. There was variability in scores across the AGREE II domains with areas covering Scope and Purpose and Clarity of Presentation scoring well. Conversely, an area needing attention was Rigour of Development. Conclusion Healthcare organisations would benefit from agreeing a ‘core content’ for the development of unlicensed medicines guidelines to ensure consistency and the presence of robust operating systems to deliver safe, effective treatment to all NHS patients.