Introduction: Most modern medical issues are inherently complicated and accurate decisions are not always likely to be made based on logical reasons. Furthermore, the huge volume of information relevant to a simple diagnostic area makes this decision making even more troublesome. Hence, with the advent of technology, there is an ever increasing need for the Clinical Decision Support System (CDSS) in hospitals. This study has been conducted in an Iranian hospital with the aim of identifying the most significant barriers for implementing CDSS and suggesting appropriate strategies to remove them.Methods: This qualitative cross-sectional study was conducted in 2015. The sample population of the study included 180 physicians and nurses in Shahid Mohammadi hospital in Bandar Abbas whose performance was changed using CDSS. The participants were selected using stratified sampling from 23 different wards in the hospital. First, the barriers and strategies for implementation of CDSS in other countries were extracted from a review study which was used to make a preliminary model. Then, the results of a questionnaire and Delphi tests in three rounds were included in the final model.Results: The most significant barriers in implementing CDSS were categorized into 6 groups according to the participants. These include barriers from human resources and infrastructures as well as financial, technical, environmental and legal ones. The barriers for them were divided into 5 categories including structural, technical, financial, human and environmental ones.Conclusion: Since the most significant obstacle in implementing CDSS in this hospital was from humans, the hospital can use the barriers provided in 5 categories and better benefit from the system. These barriers are training the human resources before they start working, engaging them in implementation process of the CDSS and using evidence-based scientific databases in CDSS while removing fundamental barriers to the system.