Abstract Background Antimicrobial resistance (AMR) is a prominent threat to public health. Although many guidelines have been developed over the years to tackle this issue, their impact on health care practice varies. Guidelines are often based on evidence from clinical trials, but these have limitations, particularly in the breadth and generalisability of the evidence and evaluation of the guidelines’ uptake. The aim of this study was to investigate how national and local guidelines for managing common infections are developed and explore guideline committee members’ opinions about using real-world observational evidence in the guideline development process. Methods Six semi-structured interviews were completed with participants who had contributed to the development or adjustment of national or local guidelines on antimicrobial prescribing over the past 5 years (from the English National Institute for Health and Care Excellence (NICE)). Interviews were audio recorded and transcribed verbatim. Data was analysed thematically. This also included review of policy documents including guidelines, reports and minutes of guideline development group meetings that were available to the public. Results Three key themes emerged through our analysis: perception versus actual guideline development process, using other types of evidence in the guideline development process, and guidelines are not enough to change antibiotic prescribing behaviour. In addition, our study was able to provide some insight between the documented and actual guideline development process within NICE, as well as how local guidelines are developed, including differences in types of evidence used. Conclusions This case study indicates that there is the potential for a wider range of evidence to be included as part of the guideline development process at both the national and local levels. There was a general agreement that the inclusion of observational data would be appropriate in enhancing the guideline development process, as well providing a potential solution for monitoring guideline use in clinical practice, and improving the implementation of treatment guidelines in primary care.