Background: Social inclusion is essential for an adequate rehabilitation process for people with serious mental illness (SMI). Various supported housing settings aim to promote housing competencies and social inclusion in service users. Nevertheless, there is a strong preference in service users for independent living. We aim to evaluate the effectiveness and efficiency of Independent Housing and Support (IHS) compared to institutionalised residential care settings and other treatment as usual conditions (RCS/TAU) in two cities in Switzerland. Methods: This is a prospective multi-centre, four-arm, non-inferiority cohort study investigating the effectiveness and efficiency of IHS and RCS/TAU for people with SMI. Effectiveness will be measured by a standardised measure of social inclusion as primary outcome as well as by measures of functioning and well-being. Efficiency will be analysed on the basis of service usage and costs associated with the different housing settings. Participants will be consecutively recruited and subsequently enrolled between April 2019 and December 2020 and assessed at baseline and after six, twelve and after 24 months. At one study site, 56 participants will be randomly assigned to one of the conditions; the other study site will be conducted as an observational study investigating 112 admitted participants. Discussion: While the UN Convention of the Rights of People with Disabilities aims to promote the opportunity to choose one's place of residence, the limited supply of alternative forms of housing does not guarantee genuine freedom of choice. Increased diversification and flexibility of housing support is essential. If IHS shows noninferiority in terms of their effectiveness and efficiency, users should be allowed to choose their kind of housing support.