The technology acceptance model (TAM) has been widely used to study user acceptance of new computer technologies. Previous studies claimed that future technology acceptance research should explore other additional explanatory variables, which may affect the originally proposed constructs of the TAM. The use of information technology in the health care sector and especially in hospitals offers great potential for improving the performance of physicians, increasing the quality of services and also reducing the organizational expenses. However, the main challenge that arises according to the literature is whether healthcare professionals are willing to adopt and use clinical information technology while performing their tasks. Although adoption of various information technologies has been studied using the technology acceptance model (TAM), the study of technology acceptance for professional groups (such as physicians) has been limited. Physician adoption of clinical information technology is important for its successful implementation. Therefore, the purpose of this study is to gain a better insight about factors affecting physicians’ acceptance of clinical decision support systems (CDSS) in a hospital setting. The results reflect the importance of perceived threat to professional autonomy, perceived interactivity with clinical IT, perceived usefulness and perceived ease of use in determining physicians’ intention to use CDSS.