Distrust of the health system is a longstanding issue for ethnoracial minorities, especially for Blacks. Not well understood, however, is the role that ethnoracial segregation within a city plays in this distrust. While segregation is typically associated with neighborhood ills, there is evidence that it can also moderate distrust. This study draws on the 2008 wave of the Public Health Management Corporation's Southeastern Pennsylvania Household Health Survey and the 2005–2009 American Community Survey to explore the possibility that segregation affects healthcare system distrust. Using hierarchical linear modeling, we find that residence in predominantly Black neighborhoods was associated with less distrust in the healthcare system for Black respondents, while residence in mixed neighborhoods was associated with more distrust for Black respondents. These findings call for a reevaluation of how healthcare system distrust is understood. Distrust has been connected to poorer health outcomes, playing into wider gaps in ethnoracial minority health outcomes.