Black women continue to be disproportionately affected by HIV with marked disparities in HIV incidence, prevalence, and care outcomes. There is a critical need to explore the role of psychosocial and structural factors and the negative impact of these factors on HIV-related outcomes, including HIV risk behaviors, HIV medication adherence, and healthcare utilization. This research uses the syndemic theory to measure the effects of both psychosocial and structural syndemics on HIV-related outcomes among Black women. Syndemic theory is a theoretical framework, which posits there are multiple, overlapping factors that form a cumulative and synergistic effect on HIV disease burden. The substance abuse, violence and AIDS (SAVA) syndemic, clustering effects of substance use, intimate partner abuse, and HIV/AIDS, have been applied in studies exploring HIV outcomes among women; however, the SAVA syndemic framework does not include additional psychosocial and structural factors such as food insecurity, housing instability, incarceration, post -traumatic stress disorder, and depression to better understand the syndemic profiles of Black women. Using study data from the HIV Prevention Trials Network 061 Women’s Seroincidence study and the Women’s Interagency HIV Study, we tested whether a cumulative syndemic of psychosocial and structural factors contributed to sexual risk behaviors and HIV care outcomes. The studies will assess three parameterizations of syndemic factors: cumulative syndemic index, syndemic group indices reflecting the level of influence (psychosocial, participant-level, and neighborhood), and number of syndemic groups (0, 1, 2, or 3). We also tested whether HIV status modified the relationships between a cumulative syndemic of psychosocial and structural factors and sexual risk behaviors. In study 1, a higher syndemic score was significantly associated with increased prevalence of unknown HIV status of last male sex partner (aPR = 1.07, 95% CI: 1.04-1.10), engaging in exchange sex (aPR = 1.17, 95% CI: 1.14-1.20), and having multiple sex partners (aPR = 1.07, 95% CI: 1.06-1.09) among a sample of 1,347 Black women. In study 2, generalized linear mixed models found that being in two syndemic groups was associated with increased odds of reporting unknown HIV status of last male sex partners (aOR=3.04, 95% CI: 1.24-7.44) and having multiple sex partners (aOR=4.29, 95% CI: 1.81-10.18) among 1,364 Black women living with and without HIV across twelve follow-up visits. We also found that being in all three syndemic groups was associated with increased odds of reporting inconsistent condom use (aOR= 2.15, 95% CI: 1.28-3.61), unknown HIV status of last male sex partners (aOR=5.26, 95% CI: 1.94-14.25), and having multiple sex partners (aOR=7.47, 95% CI: 2.85-19.58). Among a total of 969 Black women living with HIV in study 3, a higher cumulative syndemic score and a higher neighborhood-level structural syndemic group score was associated with increased odds of reporting sub-optimal HIV medication adherence (aOR=1.04, 95% CI: 1.01-1.06 and 1.08, respectively). Black women in all three syndemic groups had increased odds of reporting sub-optimal HIV medication adherence (OR=2.88, 95% CI: 1.32-6.29) and missed HIV appointments (OR=3.39, 95% CI: 1.06-10.92). Results from these studies highlight the evidence of psychosocial and structural syndemic effects on multiple HIV risk and care outcomes among Black women.