Homelessness affects HIV risk and health, but little is known about the longitudinal effects of rental assistance on the housing status and health of homeless and unstably housed people living with HIV/AIDS. Homeless/unstably housed people living with HIV/AIDS (N = 630) were randomly assigned to immediate Housing Opportunities for People with AIDS (HOPWA) rental assistance or customary care. Self-reported data, CD4, and HIV viral load were collected at baseline, 6, 12, and 18 months. Results showed that housing status improved in both groups, with greater improvement occurring in the treatment group. At 18 months, 51% of the comparison group had their own housing, limiting statistical power. Intent-to-treat analyses demonstrated significant reductions in medical care utilization and improvements in self-reported physical and mental health; significant differential change benefiting the treatment group was observed for depression and perceived stress. Significant differences between homeless and stably housed participants were found in as-treated analyses for health care utilization, mental health, and physical health. HOPWA rental assistance improves housing status and, in some cases, health outcomes of homeless and unstably housed people living with HIV/AIDS.