Pedestrians and bicyclists are the victims of countless car crashes in U.S. cities as well as around the world. Yet, many dimensions of their involvement in crashes remain rather poorly known. In this article, we follow a spatial epidemiologic approach to study the relative risk factors of bicycle and pedestrian crashes at the neighborhood level in the City of Buffalo, NY over a two-year period. The analysis examines physical road characteristics such as roadway and intersection functional classes, urban density and type of development—business or residential, as well as socio-economic and demographic variables to identify discriminating risk factors between the two non-motorized transportation modes. The analysis underscores significant differences tied to neighborhood ethnicity, educational attainment and land use, while physical characteristics of the road infrastructure register as marginally discriminating factors. Income related socio-economic status is not found to play a prominent role.