Hospital Information System (HIS) could help the delivery of high quality health services and improve patient care and patient safety. The development and the adoption of the system need to commence if high quality patient care is to be provided. However, successful HIS implementation is not an easy task and it depends on multiple factors such as adequate computer skills, lack of training and education. Despite the presence of a literature on nurse’s satisfaction on HIS, there is still a controversy over the success of HIS implementation. The input from the Information and Organisation culture, Trust and the nurses themselves, have not been considered. The aim of this study therefore, is to identify the success factors that influence a successful HIS implementation and to propose a research model which could fulfil the objective. Based on DeLone and Mc Lean's information, a success model system with an addition of four additional factors namely the Information culture, Organisational cultures, Trust and User quality was developed in this study. Employing a quantitative research methodology, this study began by conducting a pilot study involving 160 nurses from a university hospital to validate the reliability of the questionnaire to be used. Then, 1200 questionnaires were distributed to seven public university hospitals in Iran and 1028 (86%) usable responses were used for analysis. The covariance-based on structural equation modelling using STATA was employed to evaluate the model. Findings revealed that fourteen out of sixteen proposed hypotheses are significant on successful HIS implementation. The Information quality, Service quality, Organisation culture and the Information culture were among the most influential constructs in the final model. As the study was empirically tested in the Iranian setting, it contributes to theoretical and practical aspect of research especially in the Iranian public university hospital context
