Objectives: The e-prescribing risk and safety evaluation (ePRaSE) tool was developed to support the evaluation of hospital e-prescribing systems. The tool uses fictitious patients alongside previously validated prescribing scenarios to detect whether these systems provide prescribing advice to users, when completing inpatient prescribing tasks. We sought to evaluate the usability and acceptability of ePRaSE for clinical informatics pharmacy staff using different e-prescribing systems in NHS hospitals across England. Materials and methods: All NHS hospitals in England with live e-prescribing systems were invited to participate via an email invitation to the chief pharmacists. Participants were asked to complete the four-stage ePRaSE assessment, whilst verbalising their thoughts and sharing their perspectives on the acceptability and usability of the assessment. The data were transcribed verbatim, coded and analysed using the Framework Approach. Results: Ten participants from ten different hospitals across England conducted the ePRaSE assessment between April and December 2019. They completed the assessment in 2-3 hours and described the tool as easy to use and the prescribing scenarios as clinically relevant. However, some participants experienced difficulties inputting clinical data, such as laboratory results, often due to restricted access to input data into different parts of the electronic health record. Many participants suggested areas for further improvement and suggested more detailed results on completion of ePRaSE was desirable. Conclusions: E-prescribing system users found ePRaSE to be a useful and acceptable tool. Further work to refine the tool is desirable, particularly relating to the provision of results to ePRaSE users.