Reducing stigma to ensure viral load (VL) suppression for women with serious mental illness (SMI) and HIV is a global priority, including in Botswana, where the intersectional stigma of SMI, HIV and womanhood is marginalizing in ways that impede adherence to both psychiatric medications and antiretroviral therapy (ART), which can threaten VL suppression. We apply our novel ‘what matters most’ (WMM) approach to target intersectional stigma faced by women with SMI and HIV in Botswana via a stigma-reduction intervention in the high-risk transition period after discharge from an initial psychiatric hospitalization. WMM conceptualizes how stigma is felt most acutely when people are unable to achieve ‘full personhood’ by participating in the activities that ‘matter most’ in their local context. In prior research, we found the core value for ‘full womanhood’ in Botswana is achieved by being the ‘foundation of the household’ and is threatened by perceived: 1) incompetence in fulfilling the duties of a family caregiver associated with SMI and 2)  promiscuity associated with having HIV. In Botswana, family acceptance as a viable ‘family caregiver’ is also key to achieving ‘full status’ as a woman. As such, the risks of being identified as having SMI and HIV (e.g., partner/family abandonment) can deter psychiatric and ART treatment adherence. Promoting capabilities that ‘matter most’ for achieving ‘full womanhood’ could enable longer-term stigma reduction after psychiatric discharge, when women are reintegrating into their communities, and improve ART adherence and promote sustained VL suppression. Our group-based WMM stigma intervention is co-led by a peer woman who has coped effectively with SMI and HIV stigma. The WMM stigma intervention model was piloted among pregnant women with HIV in Botswana with promising reductions in stigma and depressive symptoms up to 4-months postpartum. We now test whether a WMM intervention tailored for women with SMI and HIV will reduce intersectional stigma and facilitate VL suppression. We propose a two-arm randomized controlled trial (RCT; N=180) with a 4-month follow-up to compare the effectiveness of 1) WMM-based intersectional stigma intervention delivered as clients transition from psychiatric hospitalization to outpatient care (‘WMM Stigma Intervention;’ n=90); and 2) attention control following a similar format to isolate the effects of the intervention (n=90). Because family are commonly involved in the care of people with SMI and face severe stigma, we propose a parallel, group stigma intervention among family members, as addressing familial stigma could facilitate treatment adherence. Finally, because intersectional stigma is reinforced at systemic levels, we seek to empower women with SMI and HIV to influence structural change by coleading policymaker workshops to reduce stigma among policymakers and spur policymakers to address the unique needs of women with SMI and HIV via future policies.