The authors examined associations between neighborhood-level deprivation and cardiovascular disease-related health knowledge and behavior changes, as well as the estimated 12-year probability of experiencing a coronary heart disease event. Primary analyses included multilevel regression models among 8,197 women and men living in 82 neighborhoods in four northern California cities who were interviewed in one of five surveys conducted between 1979 and 1990. After controlling for age, gender, marital status, race/ethnicity, city, and time, the authors found that adults living in high-deprivation neighborhoods had significantly lower health knowledge and a higher probability of no positive behavior changes than did adults in moderately deprived neighborhoods (i.e., harmful effects). Conversely, those living in low-deprivation neighborhoods had significantly higher health knowledge and lower probabilities of no positive behavior changes and estimated risk of coronary heart disease (i.e., protective effects). The association between high neighborhood deprivation and no positive behavior changes remained statistically significant after additional adjustment for a composite measure of individual-level socioeconomic status. Associations with neighborhood deprivation did not vary by individual-level socioeconomic status. These results suggest that focusing exclusively on changing individuals' behaviors will have a limited effect unless contextual influences at the neighborhood level are also addressed.