Objectives: For more than three decades there has been speculation regarding a possible role of zoonotic diseases in the development of human leukemia. This study investigated the potential relationship between exposure to pets and the development of childhood leukemia. Methods: Data from 2359 cases of acute leukemia from two large case–control studies were analyzed. Cases were individually matched to population controls on telephone exchange, age, and race. Conditional logistic regression was used to estimate odds ratios (OR) associated with pet ownership. Results: Overall, there was no association between pet ownership (either “any pet”, dog, or cat) and childhood acute leukemia (ORany pet:=1.01, 95% CI 0.89–1.2). Additionally, no relationship was found between exposure to an ill pet and childhood leukemia. Conclusion: The results of this analysis suggest that pet ownership (healthy or sick) is unrelated to an increased risk of childhood leukemia.