Background The need for information exchange and integrated care has stimulated the development of interoperability solutions that bring together patient data across the health and care system to enable effective information sharing. Health Information Exchange (HIE) solutions have been shown to be effective in supporting patient care, however, user adoption often varies among users and care settings. This service evaluation aimed to measure user acceptance of HIE and explore barriers and facilitators to its wider uptake. Methods A mixed-method study design was used. A questionnaire was developed using the Unified Theory of Acceptance and Use of Technology and administered to HIE users to assess technology acceptance. Pearson Chi² tests were used to examine differences in acceptance between user groups and care settings. Web-based, semi-structured interviews were conducted drawing on the Normalisation Process Theory to explore barriers and facilitators to adoption. Interview data were analysed thematically using the Framework Approach. Results A total of 105 HIE users completed the survey and another 12 participated in the interviews. Significant differences were found in HIE acceptance between users groups and care settings, with high adopters demonstrating higher acceptance and social care users showing lower acceptance. Participants identified several drivers to adoption, including increased information accessibility, better care coordination, informed decision-making, improved patient care, reduced duplication of procedures, and time and cost savings. However, they also highlighted a number of barriers, such as lack of awareness about the solution and its value, suboptimal communication strategies, inadequate training and lack of resources for knowledge dissemination, absence of champions to support the implementation, lack of end-user involvement in the implementation and evaluation of HIE, unclear accountability and responsibility for the overall success of the programme, and patient confidentiality concerns. Conclusions Working to better engage stakeholders, considering the needs of users from different care settings, providing users with training resources and support to increase their knowledge and confidence in using the system, developing implementation strategies to seek user feedback and monitor performance, and using communication strategies to increase awareness of the product and its value, can help improve uptake and adoption of HIE.