The “thrifty genotype hypothesis” has become firmly entrenched as one of the orienting concepts in biomedical anthropology, since first being proposed by Neel (1962 Am. J. Hum. Genet. 14:353–362) over 40 years ago. Its influence on inquiries into the evolutionary origins of diabetes, lactose tolerance, and other metabolic disorders can hardly be underestimated, as evidenced by its continued citation in many top scientific and medical journals. However, its fundamental assumption, that foragers are more likely to experience regular and severe food shortages than sedentary agriculturalists, remains largely untested. The present report tests this assumption by making a cross-cultural statistical comparison of the quantity of available food and the frequency and extent of food shortages among 94 foraging and agricultural societies as reported in the ethnographic record. Our results indicate that there is no statistical difference (P < 0.05) in the quantity of available food, or the frequency or extent of food shortages in these reports between preindustrial foragers, recent foragers, and agriculturalists. The findings presented here add to a growing literature that calls into question assumptions about forager food insecurity and nutritional status in general, and ultimately, the very foundation of the thrifty genotype hypothesis: the presumed food shortages that selected for a “thrifty” metabolism in past foraging populations. Am J Phys Anthropol, 2006. © 2005 Wiley-Liss, Inc.