Housing First is an approach to ending homelessness that recognizes permanent housing as a platform for stability and engagement in health services. As part of a randomized controlled trial to test the effects of permanent supportive housing with the Housing First approach in Denver, Colorado, we analyzed the intervention's impact on health care use, Medicaid enrollment, and mortality among people experiencing chronic homelessness who had frequent arrests and jail stays. Two years after assignment to the Housing First intervention, participants had an average of eight more office-based visits for psychiatric diagnoses, three more prescription medications, and six fewer emergency department visits than the control group. Although enrollment in Medicaid increased over the course of the study for both the intervention group and the control group, the intervention group was 5 percentage points less likely to be enrolled in Medicaid. Supportive housing had no significant impact on mortality. When considering pathways to scale up supportive housing, policy makers should recognize the potential of Housing First to facilitate the use of office-based psychiatric care and medications in a population with many health care needs.