OBJECTIVE: The ubiquity of cribra orbitalia in skeletal samples has led to rigorous debate over their etiology, with most concluding that nutrition, physiological stressors, and environmental disease vectors synergistically contribute to lesion development. To parse the relative contributions of these etiological factors in the prehistoric Andes, this spatial paleopathological meta-analysis investigates the relationship between population-wide prehistoric Andean cribra orbitalia rates and geographic, climatic, and hydrological variables. METHODS: Crude prevalence patterns of cribra orbitalia from 61 archaeological sites were plotted and analyzed with geostatistical methods to explore spatial patterns in the distribution of anemia-associated lesions. Multiple linear regression modeling was performed on 19 spatial variables suspected to contribute to various forms of anemia that result in cribrotic lesions. RESULTS: Spatially-clustered high cribra orbitalia rates exist around the Central Peruvian coast, but are paradoxically low on the Ecuadorian coast. Multiple regression shows that elevation, temperature, and precipitation were not predictive of lesion rates. Multiple regression models show that aridity and seasonal variability in freshwater supply, together, explained a third of the variation in lesion rates. CONCLUSION: While cribra orbitalia has long been tied to coastal proximity, these results suggest environmental constraints such as the need for water storage could have promoted malnutrition and pathogenic infection more than mere coastal proximity. LIMITATIONS OF THIS STUDY: This analysis is limited by the paucity of data from highland sites and by the assumption that burials are local to the excavation site. SUGGESTIONS FOR FUTURE RESEARCH: Future studies will integrate isotopic and remotely-sensed data into models to explore links between water security, nutrition, and disease.