Objectives: To strengthen existing evidence on the role of neighborhoods in chronic disease onset in later life, we investigated associations between multiple neighborhood features and 2-year onset of 6 common conditions using a national sample of older adults. Methods: Neighborhood features for adults aged 55 years or older in the 2002 Health and Retirement Study were measured by use of previously validated scales reflecting the built, social, and economic environment. Two-level randomintercept logistic models predicting the onset of heart problems, hypertension, stroke, diabetes, cancer, and arthritis by 2004 were estimated. Results: In adjusted models, living in more economically disadvantaged areas predicted the onset of heart problems for women (odds ratio [OR]=1.20; P<.05). Living in more highly segregated, higher-crime areas was associated with greater chances of developing cancer for men (OR=1.31; P<.05) and women (OR=1.25; P<.05). Conclusions: The neighborhood economic environment is associated with heart disease onset for women, and neighborhood-level social stressors are associated with cancer onset for men and women. The social and biological mechanisms that underlie these associations require further investigation.