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Background and Aim: Hospital Information Systems (HIS) are used for easy access to information, improvement of documentation and reducing errors. Nonetheless, using these systems is faced with some barriers and obstacles. This study identifies the challenges and the obstacles of using these systems in the academic and non-academic hospitals in Kerman., Methods: This is a cross-sectional study which was carried out in 2015. The statistical population in this study consisted of the nurses who had been working in the academic and non-academic hospitals in Kerman. A questionnaire consisting of two sections was used. The first section consisted of the demographic information of the participants and the second section comprised 34 questions about the challenges of HIS use. Data were analyzed by the descriptive and statistical analysis (t-test, and ANOVA) using SPSS 19 software., Results: The most common and important challenges in the academic hospitals were about human environment factors, particularly "negative attitude of society toward using HIS". In the non-academic hospitals, the most common and important challenges were related to human factors, and among them, "no incentive to use system" was the main factor. The results of the t-test method revealed that there was a significant relationship between gender and the mean score of challenges related to the organizational environment category in the academic hospitals and between familiarity with HIS and mean score of human environment factors (p<0.05). The results of the ANOVA test also revealed that the educational degree and work experience in the healthcare environment (years) in the academic hospitals have a significant relationship with the mean score related to the hardware challenges, as well, experience with HIS has a significant relationship, with the mean score related to the human challenges (p<0.05)., Conclusion: The most important challenges in using the information systems are the factors related to the human environment and the human factors. The results of this study can bring a good perspective to the policy makers and the managers regarding obstacles of using HISs from the nurses' perspective, so that they can solve their problems and can successfully implement these systems., Competing Interests: Conflict of Interest: There is no conflict of interest to be declared.