Background Measures of socioeconomic disadvantage may enable improved targeting of programs to prevent rehospitalizations, but obtaining such information directly from patients can be difficult. Measures of US neighborhood socioeconomic disadvantage are more readily available, although rarely employed clinically. Objective To evaluate the association between neighborhood socioeconomic disadvantage at the census block-group level, as measured by Singh’s validated Area Deprivation Index (ADI), and 30-day rehospitalization. Design Retrospective cohort study Setting United States Patients Random 5% national sample of fee-for-service Medicare patients discharged with congestive heart failure, pneumonia or myocardial infarction, 2004–2009 (N = 255,744) Measurements 30-day rehospitalizations. Medicare data were linked to 2000 Census data to construct an ADI for each patient’s census block-group, which were then sorted into percentiles by increasing ADI. Relationships between neighborhood ADI grouping and rehospitalization were evaluated using multivariate logistic regression models, controlling for patient sociodemographics, comorbidities/severity, and index hospital characteristics. Results The 30-day rehospitalization rate did not vary significantly across the least disadvantaged 85% of neighborhoods, which had an average rehospitalization rate=21%. However, within the most disadvantaged 15% of neighborhoods, rehospitalization rates rose from 22% to 27% with worsening ADI. This relationship persisted after full adjustment, with the most disadvantaged neighborhoods having a rehospitalization risk (adjusted risk ratio = 1.09, confidence interval 1.05–1.12) similar to that of chronic pulmonary disease (1.06, 1.04–1.08) and greater than that of diabetes (0.95, 0.94–0.97). Limitations No direct markers of care quality, access Conclusions Residence within a disadvantaged US neighborhood is a rehospitalization predictor of magnitude similar to chronic pulmonary disease. Measures of neighborhood disadvantage, like the ADI, could potentially be used to inform policy and post-hospital care. Primary Funding Source National Institute on Aging