ABSTRACT Structural racism is a fundamental cause of the persistent and pervasive racial/ethnic inequities in mortality. Minoritized racial/ethnic groups experience structural racism via a system of mutually reinforcing institutions that perpetuates inequities in health through policies, practices, and norms across the domains of housing, education, employment, criminal justice, political participation, and healthcare. Yet, few studies have investigated the contribution of mutually reinforcing institutions across multiple domains of structural racism on inequities in mortality for multiple minoritized racial/ethnic populations. We propose to investigate the impact of multiple domains of structural racism on racial/ethnic-specific mortality for Black (n=30,834), Hispanic/ Latino (n=43,538), Japanese American (n=45,115) and Native Hawaiian (n=8,202) adults in the Multiethnic Cohort (MEC) Study using novel, racial/ethnic-specific composite measures of structural racism at the geographic level of city, town, or Census designated place. The composite measure will include indicators from multiple domains including housing, education, employment, criminal justice, political participation and health care. Specifically we aim to examine the impact of these composite measures of structural racism on all- cause mortality (Aim 1) and cause-specific mortality (Aim 2) for Black, Hispanic/Latino, Japanese American, and Native Hawaiian participants in the MEC and estimate years of life lost due to structural racism. In addition, we will use causal inference methods to investigate whether neighborhood disinvestment, discrimination, social support, health behaviors, and comorbidities mediate the associations between structural racism and mortality, and investigate these associations across subgroups defined by sex, life stage, and socioeconomic status. We will seek guidance from a multidisciplinary External Advisory Board and regional and racial/ethnic-specific Community Advisory Boards in the development of composite measures of structural racism, interpretation of study findings, and dissemination of the study measures and results. The findings from the proposed study will provide key evidence of the specific interacting institutions that should be targeted to improve the lifespan for Black, Hispanic/Latino, Japanese American, and Native Hawaiian populations. The impact of this research is high as it will have translational relevance in providing empirical evidence for community stakeholders, policy makers, and implementation scientists to direct interventions for reducing premature mortality specific to minoritized racial/ethnic groups.