IntroductionHousing First is a complex housing and support intervention for homeless individuals with mental health problems. It has a sufficient knowledge base and interest to warrant a test of wide-scale implementation in various settings. This protocol describes the quantitative design of a Canadian five city, $110 million demonstration project and provides the rationale for key scientific decisions.MethodsA pragmatic, mixed methods, multi-site field trial of the effectiveness of Housing First in Vancouver, Winnipeg, Toronto, Montreal and Moncton, is randomising approximately 2500 participants, stratified by high and moderate need levels, into intervention and treatment as usual groups. Quantitative outcome measures are being collected over a 2-year period and a qualitative process evaluation is being completed. Primary outcomes are housing stability, social functioning and, for the economic analyses, quality of life. Hierarchical linear modelling is the primary data analytic strategy.Ethics and disseminationResearch ethics board approval has been obtained from 11 institutions and a safety and adverse events committee is in place. The results of the multi-site analyses of outcomes at 12 months and 2 years will be reported in a series of core scientific journal papers. Extensive knowledge exchange activities with non-academic audiences will occur throughout the duration of the project.Trial registration numberThis study has been registered with the International Standard Randomised Control Trial Number Register and assigned ISRCTN42520374.

Housing First with ACT is an effective approach in various contexts for assisting individuals with serious mental illness to rapidly exit homelessness.

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Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways.