Background Medical mistrust is a barrier to engaging in HIV prevention and treatment, including testing and adherence to antiretroviral therapy. Research often focuses on how race and experiences of discrimination relate to medical mistrust, overlooking the role that other characteristics may play (e.g., history of physical abuse, diagnosis of mental illness). Furthermore, studies are often restricted to samples of men who have sex with men and findings may not generalize to other at-risk groups. Aims The current study explores a range of demographic, cognitive, behavioral, and social network correlates of medical mistrust. Method This study employed an egocentric network design among a racially diverse sample of at-risk women and women in their social networks ( n = 165). Results Results from multivariable linear regressions stratified by race (Black vs. others) indicate that medical mistrust is associated with both individual-level and network-level characteristics. Across both groups, age and experiences of racial discrimination were associated with higher medical mistrust. Having a regular sex partner and having a higher proportion of network members who are family was significantly associated with medical mistrust among non-Black women. Discussion Individual-level and network-level variables were significantly associated with medical mistrust. Therefore, interventions that attempt to mitigate medical mistrust as a barrier to HIV prevention and treatment should consider how mistrust may be related to characteristics of individuals and broader contexts. Conclusion Health interventions may benefit from conceiving of medical mistrust as a complex, rational response to cumulative discriminatory life experiences and a reflection of the networks within which individuals are embedded.