BACKGROUND: Antipsychotic prescribing is prevalent in nursing homes for the management of behavioral and psychological symptoms of dementia (BPSD), despite the known risks and limited effectiveness. Many studies have attempted to understand this continuing phenomenon, using qualitative research methods, and have generated varied and sometimes conflicting findings. To date, the totality of this qualitative evidence has not been systematically collated and synthesized. AIMS: To synthesize the findings from individual qualitative studies on decision-making and prescribing behaviors for antipsychotics in nursing home residents with dementia, with a view to informing intervention development and quality improvement in this field. METHODS: A systematic review and synthesis of qualitative evidence was conducted (PROSPERO protocol registration CRD42015029141). Six electronic databases were searched systematically from inception through July 2016 and supplemented by citation, reference, and gray literature searching. Studies were included if they used qualitative methods for both data collection and analysis, and explored antipsychotic prescribing in nursing homes for the purpose of managing BPSD. The Critical Appraisal Skills Program assessment tool was used for quality appraisal. A meta-ethnography was conducted to synthesize included studies. The Confidence in the Evidence from Reviews of Qualitative research approach was used to assess the confidence in individual review findings. All stages were conducted by at least 2 independent reviewers. RESULTS: Of 1534 unique records identified, 18 met the inclusion criteria. Five key concepts emerged as influencing decision-making: organizational capacity; individual professional capability; communication and collaboration; attitudes; regulations and guidelines. A "line of argument" was synthesized and a conceptual model constructed, comparing this decision-making process to a dysfunctional negative feedback loop. Our synthesis indicates that when all stakeholders come together to communicate and collaborate as equal and empowered partners, this can result in a successful reduction in inappropriate antipsychotic prescribing. CONCLUSIONS: Antipsychotic prescribing in nursing home residents with dementia occurs in a complex environment involving the interplay of various stakeholders, the nursing home organization, and external influences. To improve the quality of antipsychotic prescribing in this cohort, a more holistic approach to BPSD management is required. Although we have found the issue of antipsychotic prescribing has been extensively explored using qualitative methods, there remains a need for research focusing on how best to change the prescribing behaviors identified.