Purpose: To examine how the choice of neighborhood food environment definition impacts the association with diet. Methods: Using food frequency questionnaire data from the Reasons for Geographic and Racial Differences in Stroke study at baseline (2003–2007), we calculated participants’ dietary inflammation score (DIS) (n = 20,331); higher scores indicate greater pro-inflammatory exposure. We characterized availability of supermarkets and fast food restaurants using several geospatial measures, including density (i.e., counts/km2) and relative measures (i.e., percentage of all food stores or restaurants); and various buffer distances, including administrative units (census tract) and empirically derived buffers (“classic” network, “sausage” network) tailored to community type (higher density urban, lower density urban, suburban/small town, rural). Using generalized estimating equations, we estimated the association between each geospatial measure and DIS, controlling for individual- and neighborhood-level sociodemographics. Results: The choice of buffer-based measure did not change the direction or magnitude of associations with DIS. Effect estimates derived from administrative units were smaller than those derived from tailored empirically derived buffer measures. Substantively, a 10% increase in the percentage of fast food restaurants using a “classic” network buffer was associated with a 6.3 (SE = 1.17) point higher DIS (P< .001). The relationship between the percentage of supermarkets and DIS, however, was null. We observed high correlation coefficients between buffer-based density measures of supermarkets and fast food restaurants (r = 0.73–0.83), which made it difficult to estimate independent associations by food outlet type. Conclusions: Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures.