The SANTINELLES project in Saint Louis, Senegal and Bobo Dioulasso, Burkina Faso sought to measure spatial health disparities and to understand them in the context of the physical environment, but also in regards to the social, economic, and historic processes in each city. We aspired to compare the presence and severity of health inequalities among neighborhoods in each city as well as between the two cities, rather than comparing the overall prevalence of disease in each city. Our key health indicators included malaria, anthropod-borne viruses, arterial hypertension, diabetes, nutritional status, anemia, and access to medical care. Our findings indicate that infectious and parasitic diseases remain significant in these urban settings, but non-communicable diseases were also important. We found significant health disparities among the neighborhoods in each city and important differences in the disease burdens of the two cities. The double burden of chronic and infectious diseases is challenging not only to individuals, but also to households that are faced with making difficult financial trade-offs to access medical care.