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"Background Employment improves mental health and well-being by providing financial security, daily structure, a sense of identity and purpose, and social engagement. However, securing and sustaining employment is exceptionally challenging for vulnerable populations who experience persistent and multiple barriers, such as mental illness, homelessness, food and housing insecurity, and marginalization. Evidence-based supported employment programs, most notably individual placement and support (IPS) are becoming a more common approach for addressing the needs of these high-risk individuals. The aim of this paper is to outline the protocol for evaluating an IPS program in Vancouver’s downtown and Downtown Eastside (DTES). Methods and design This prospective quasi-experimental study of persons with persistent and multiple barriers to employment will use a mixed-methods approach for evaluating a novel IPS program. The evaluation will consist of survey packages and interviews that will capture outcomes related to employment and well-being, as well as the experiential process of receiving individualized and integrated supports through the IPS program. A mixed-methods approach is appropriate for this study as quantitative data will provide an objective assessment of program impacts on employment and well-being outcomes over time, while qualitative data will provide an in-depth understanding of continued barriers and experiences. Discussion The results from this evaluation will contribute evidence within a local British Columbian (BC) context that may increase access to meaningful employment for those with long-term experience of complex barriers to employment. Further, the findings will support continued improvements, and guide decision-making around practices and policy for future implementation of IPS and employment supports across BC."