Structural Ecosystems Therapy (SET) is an intervention designed to mobilize participants’ families and other ecosystem members (such as service providers) to support and motivate behavior change. In this study, the SET intervention was adapted with the goal of reducing HIV transmission risk behavior and increasing medical adherence among HIV+ men being released from prison. In the intervention, participants and their ecosystem members met with the intervention staff in sessions designed to restructure interactions and communication patterns among ecosystem members with the goal of supporting participants’ positive behavior change. We recruited a total of 162 men from San Quentin State Prison, the California Medical Facility (CMF), and San Francisco County Jail. Participants were randomly assigned to receive either SET or an individually-focused comparison intervention that reduced sexual risk behavior in a previous study. Each intervention was four months in length. Participants were assessed before treatment, and at four, eight and twelve months after their release from prison.