Evidence of the association between income inequality and mortality has been mixed. Studies indicate that growing income inequalities reflect inequalities between, rather than within, racial groups. Racial segregation may play a role. We examine the role of racial segregation on the relationship between income inequality and mortality in a cross-section of US metropolitan areas. Metropolitan areas were included if they had a population of at least 100,000 and were at least 10% black (N = 107). Deaths for the time period 1991-1999 were used to calculate age-adjusted all-cause mortality rates for each metropolitan statistical area (MSA) using direct age-adjustment techniques. Multivariate least squares regression was used to examine associations for the total sample and for blacks and whites separately. Income inequality was associated with lower mortality rates among whites and higher mortality rates among blacks. There was a significant interaction between income inequality and racial segregation. A significant graded inverse income inequality/mortality association was found for MSAs with higher versus lower levels of black-white racial segregation. Effects were stronger among whites than among blacks. A positive income inequality/mortality association was found in MSAs with higher versus lower levels of Hispanic-white segregation. Uncertainty regarding the income inequality/mortality association found in previous studies may be related to the omission of important variables such as racial segregation that modify associations differently between groups. Research is needed to further elucidate the risk and protective effects of racial segregation across groups.