Introducing technological change to an organization’s normal processes can potentially bring about positive or negative results, depending mostly on the manner in which the change was facilitated and integrated into the organization. However, very little research has been done on information technology (IT) investment among hospitals, its effect on the personnel, as well as how it influences patient care and financial performance. Consequently, little is known about users’ resistance to new technologies and the precedents of technology rejection in healthcare. Therefore, this study seeks to fill the gap of understanding South African hospital staffs’ perceptions towards change, caused by introducing an information system into one of the hospital’s daily processes. Where resistance towards change is identified, the study aims to understand the reasons behind such resistance. Finally, it aims to find appropriate intervention strategies to deal with and minimize resistance. In doing so, the study seeks to contribute to the body of research regarding change resistance to information systems in public South African hospitals. By adopting a descriptive and exploratory interpretivist paradigm, in conjunction with an inductive approach, the study aims to get a better understanding of hospital staffs’ perceptions through shared meaning. The study adopted a case study research strategy, as it affords the researcher the opportunity to participate in the study, and as such contributes to the subjective interpretation of the findings. Data was collected using a mixed method approach, and was used to describe the difference between the current and proposed process. In addition, it was used to explore the reasons for change resistance to information system-supported change, and to explore methods of successfully introducing change to tertiary public hospitals in South Africa. Fourteen participants (7 medical interns and 7 ward clerks) who were directly involved in the process being studied, were interviewed. Two other participants (the head of the pharmacy and the patient flow manager), who were indirectly involved in the process, were interviewed, to verify the observed and mapped process. Interview data was analyzed qualitatively, firstly through coding techniques before using sentiment and thematic analysis. While the mapped process followed Business Process Modelling Notation conventions. In addition to a mapped proposed process, a change resistance conceptual model was developed from a conjunction of the findings and extensive review of literature. The conceptual model asserts that five main factors contribute to change resistance: unclearly defined duties; fear of job security and technology usage; years of service; resource availability and resource mismatch; as well as insufficient training resulting from the lack of a learning culture. These factors can be moderated by: the existing state of affairs referred to as status quo; management involvement; and communication. The conceptual model can be used to better understand the causes of change resistance, as well as how to minimize change resistance and successfully introduce change into a health organization. Change agents should aim to understand the status quo that exists in the organization and find ways of incorporating that into the change process. Furthermore, management should aim to involve and communicate with all affected stakeholders during a change process. This research has provided a better understanding of hospital staffs’ reactions to change, their reasons for resistance, and ways to minimize change resistance while successfully introducing change into a health organization.