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Background. Antimicrobial use in acute care is widely reported to be suboptimal. Inappropriate use of antimicrobials is a major contributing factor to the emergence of multidrug resistance and health care–associated infection. Addressing prescribing behavior is a key component of antimicrobial stewardship.Methods. We performed a novel systematic review of both qualitative and quantitative literature on antimicrobial prescribing behavior in acute care. We assessed the extent to which behavioral sciences and social marketing were used and whether this could be related to the effectiveness of reported outcomes. MEDLINE, Excerpta Medica Database (EMBASE), Applied Social Sciences Index and Abstracts (ASSIA), Business Source Complete, The Cochrane Library, PsychInfo, Database of Abstracts of Reviews of Effectiveness (DARE) and Health Management Information Consortium (HMIC) were searched for studies undertaken during the period January 1999–April 2011 and published in English.Results. Five qualitative and 5 quantitative studies met the quality criteria. Qualitative studies highlight the predominant influence of social norms, attitudes, and beliefs on antimicrobial prescribing behavior. Quantitative studies reporting interventions to optimize antimicrobial prescribing behavior do not use theoretical science or primary research to inform the design and choice of the interventions deployed.Conclusions. Despite qualitative evidence demonstrating the impact of behavioral determinants and social norms on prescribing, these influences are not given due consideration in the design and evaluation of interventions. To ensure a better understanding of prescribing behaviors and to improve the quality of interventions and research in this area, the incorporation and application of behavioral sciences supported by appropriate multidisciplinary collaboration is recommended.