Economic differences and proximal risk factors do not fully explain the persistent high infant mortality rates of African Americans (blacks). The authors hypothesized that racial residential segregation plays an independent role in high black infant mortality rates. Segregation restricts social and economic advantage and imposes negative environmental exposures that black women and infants experience. The study sample was obtained from the 2000-2002 US Linked Birth/Infant Death records and included 677,777 black infants residing in 64 cities with 250,000 or more residents. Outcomes were rates of all-cause infant mortality, postneonatal mortality, and external causes of death. Segregation was measured by using the isolation index (dichotomized at 0.60) from the 2000 US Census Housing Patterns. Propensity score matching methods were used. After matching on propensity scores, no independent effect of segregation on black infant mortality rates was found. Results show little statistical evidence that segregation plays an independent role in black infant mortality. However, a key finding is that it is difficult to disentangle contextual effects from the characteristics of individuals.