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.