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Childhood leukemia etiology, and mainly the interactions of genetic and environmental risk factors, remains largely unexplored. This national hospital-based case–control study was carried out in Brazil among children aged 0–23 months who were recruited at cancer and general hospitals in 13 states. Maternal medicine intake during pregnancy, including analgesic intake, was assessed by face-to-face interviews with the mothers of 231 leukemia patients and 411 controls. Unconditional logistic regression was used to ascertain crude and adjusted odds ratios (ORs), and their 95% confidence intervals (CIs) for the association between maternal analgesic use during pregnancy and early age leukemia. Acetaminophen use during the first trimester of pregnancy showed an OR=0.39 (95% CI 0.17–0.93) for acute lymphocytic leukemia and an OR=0.37 (95% CI 0.16–0.88) for use in the second trimester. For acute myeloid leukemia, an OR=0.11 (95% CI 0.02–0.97) was found following acetaminophen use in the second trimester. For acute lymphocytic leukemia, the exclusive use of dipyrone during preconception showed an OR=1.63 (95% CI 1.06–2.53) and dipyrone intake during lactation showed an OR=2.00 (95% CI 1.18–3.39). These results suggest that acetaminophen use during pregnancy may protect against development of early age leukemia in the offspring, whereas dipyrone use may act as a risk factor for such an outcome.