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Background: Antibiotic resistance is a major health threat. Inappropriate antibiotic use has been shown to be an important determinant of the emergence of antibiotic resistance. Decision support systems for antimicrobial management can support clinicians to optimize antibiotic prescription. Objective: The aim of this systematic review is to identify factors influencing the implementation of decision support systems for antibiotic prescription in hospitals. Methods: A systematic search of factors impeding or facilitating successful implementation of decision support systems for antibiotic prescription was performed in January 2022 in the databases PubMed, Web of Science and The Cochrane Library. Only studies were included which comprised decision support systems in hospitals for prescribing antibiotic therapy, published in English with a qualitative, quantitative or mixed-methods study design and between 2011 and 2021. Factors influencing the implementation were identified through text analysis by two reviewers. Results: A total of 14 publications were identified matching the inclusion criteria. The majority of factors relate to technological and organizational aspects of decision support system implementation. Some factors include the integration of the decision support systems into existing systems, system design, consideration of potential end-users as well as training and support for end-users. In addition, user-related factors, like user attitude towards the system, computer literacy and prior experience with the system seem to be important for successful implementation of decision support systems for antibiotic prescription in hospitals. Conclusion: The results indicate a broad spectrum of factors of decision support system implementation for antibiotic prescription and contributes to the literature by identifying important organizational as well as user-related factors. Wider organizational dimensions as well as the interaction between user and technology appear important for supporting implementation. [ABSTRACT FROM AUTHOR]