© 2014, Society of General Internal Medicine. BACKGROUND: While most organizational literature has focused on initiatives that transpire inside the hospital walls, the redesign of American health care increasingly asks that health care institutions address matters outside their walls, targeting the health of populations. The US Department of Veterans Affairs (VA)’s national effort to end Veteran homelessness represents an externally focused organizational endeavor.OBJECTIVE: Our aim was to evaluate the role of organizational practices in the implementation of Housing First (HF), an evidence-based homeless intervention for chronically homeless individuals.DESIGN: This was an interview-based comparative case study conducted across eight VA Medical Centers (VAMCs).PARTICIPANTS: Front line staff, mid-level managers, and senior leaders at VA Medical Centers were interviewed between February and December 2012.APPROACH: Using a structured narrative and numeric scoring, we assessed the correlation between successful HF implementation and organizational practices devised according to the organizational transformation model (OTM).CONCLUSION: Key organizational practices correlated with more successful implementation of HF for homeless Veterans. Medical Center directors substantively influenced the success of this endeavor through their actions to foster impetus, demonstrate commitment and support alignment and integration.KEY RESULTS: Scoring results suggested a strong association between HF implementation and OTM practice. Strong impetus to house Veterans came from national leadership, reinforced by Medical Center directors closely tracking results. More effective Medical Center leaders differentiated themselves by joining front-line staff in the work (at public events and in process improvement exercises), by elevating homeless-knowledgeable persons into senior leadership, and by exerting themselves to resolve logistic challenges. Vertical alignment and horizontal integration advanced at sites that fostered work groups cutting across service lines and hierarchical levels. By contrast, weak alignment from top to bottom typically also hindered cooperation across departments. Staff commitment to ending homelessness was high, though sustainability planning was limited in this baseline year of observation.