Background Residential segregation has been identified as drivers of disparities in health outcomes, but further work is needed to understand this association with clinical outcomes for out-of-hospital cardiac arrest (OHCA). We utilized Cardiac Arrest Registry to Enhance Survival (CARES) dataset to examine if there are differences in survival to discharge and survival with good neurological outcome, as well as likelihood of bystander CPR, using validated measures of racial, ethnic, and economic segregation. Methods We conducted a retrospective observational study using data from the Cardiac Arrest Registry to Enhance Survival (CARES) dataset to examine associations among adult OHCA patients. The primary predictor was the Index of Concentration at the Extremes (ICE), a validated measure that includes race, ethnicity, and income across three measures at the census tract level. The primary outcomes were survival to discharge and survival with good neurological status. A multivariable modified Poisson regression modeling approach with random effects at the EMS agency and hospital level was utilized. Results We identified 626,264 OHCA patients during the study period. The mean age was 62 years old (SD 17.2 years), and 35.7% (n =223,839) of the patients were female. In multivariable models, we observed an increased likelihood of survival to discharge and survival with good neurological outcome for those patients residing in predominately White population census tracts and higher income census tracts as compared to lower income Black and Hispanic/Latinx population census tracts (RR 1.24, CI 1.20-1.28) and a 32% increased likelihood of receiving bystander CPR in higher income census tracts as compared to reference (RR 1.32, CI 1.30-1.34). Conclusions In this study examining the association of measures of residential segregation and OHCA outcomes, there was an increased likelihood of survival to discharge, survival with good neurological status, and likelihood of receiving B-CPR for those patients residing in predominately White population and higher income census tracts when compared to predominately Black and/or Hispanic Latinx populations and lower income census tracts. This research suggests that areas impacted by residential and economic segregation are important targets for both public policy interventions as well as addressing disparities in care across the chain of survival for OHCA.