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Energy balance is relevant to diverse issues in ecology, physiology, and evolution. To determine whether lizards are generally in positive energy balance, we synthesized a massive data set on the proportion of individual lizards (N = 18 223) with empty stomachs (127 species), representing nine families distributed on four continents, primarily in temperate zone deserts but also in the neotropics. The average percentage of individuals with empty stomachs is low (13.2%) across all species, even among desert lizards, suggesting that most lizards are in positive energy balance. Nevertheless, species vary substantially in this regard (among all species, 0% to 66% of individuals have empty stomachs). Several patterns are detectable among species with unusually high frequencies of empty stomachs. In particular, nocturnal lizards "run on empty" more often on average than do diurnal species (24.1% vs. 10.5%); and this pattern holds even for nocturnal vs. diurnal geckos (21.2% vs. 7.2%, respectively). Several (but not all) top predators have a higher frequency of empty stomachs than do species that feed at lower trophic levels. Diet breadth and body size appear unrelated to frequency of empty stomachs. Widely foraging species sometimes have a high frequency of empty stomachs relative to sit-and-wait species, but patterns vary among continents and appear to be confounded by phylogeny and trophic level. Ant-eating specialists have uniformly low frequencies of empty stomachs. Diurnal termite specialists also have low frequencies of empty stomachs, but nocturnal ones have high frequencies. Lizards from certain families (Gekkonidae [including Pygopodidae],Gymnophthlamidae, and Varanidae) are more likely to have empty stomachs than an those of other families (Agamidae, Iguanidae, Lacertidae, Scincidae, and Teiidae).