Background: Neighborhood-level characteristics such as economic hardship and the retail food environment are assumed to be correlated and to influence consumers' dietary behavior and health status, but few studies have investigated these different relationships comprehensively in a single study. This work aims to investigate the association between neighborhood-level economic hardship, the retail food environment, fast food consumption, and obesity prevalence. Methods: Linking data from the population-based Survey of the Health of Wisconsin (SHOW, n = 1,570, 2008-10) and a commercially available business database, the Wisconsin Retail Food Environment Index (WRFEI) was defined as the mean distance from each participating household to the three closest supermarkets divided by the mean distance to the three closest convenience stores or fast food restaurants. Based on US census data, neighborhood-level economic hardship was defined by the Economic Hardship Index (EHI). Relationships were analyzed using multivariate linear and logistic regression models. Results: SHOW residents living in neighborhoods with the highest economic hardship faced a less favorable retail food environment (WRFEI = 2.53) than residents from neighborhoods with the lowest economic hardship (WRFEI = 1.77; p-trend < 0.01). We found no consistent or significant associations between the WRFEI and obesity and only a weak borderline-significant association between access to fast food restaurants and self-reported fast food consumption (≥2 times/week, OR = 0.59-0.62, p = 0.05-0.09) in urban residents. Participants reporting higher frequency of fast food consumption (≥2 times vs. <2 times per week) were more likely to be obese (OR = 1.35, p = 0.06). Conclusion: This study indicates that neighborhood-level economic hardship is associated with an unfavorable retail food environment. However inconsistent or non-significant relationships between the retail food environment, fast food consumption, and obesity were observed. More research is needed to enhance methodological approaches to assess the retail food environment and to understand the complex relationship between neighborhood characteristics, health behaviors, and health outcomes.