Objective: Utilizing data from the largest study to date, we examined associations between maternal preconception/prenatal exposure to household chemicals and infant acute leukemia. Methods: We present data from a Children's Oncology Group case-control study of 443 infants (\1 year of age) diagnosed with acute leukemia [including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)] between 1996 and 2006 and 324 population controls. Mothers recalled household chemical use 1 month before and throughout pregnancy. We used unconditional logistic regression adjusted for birth year, maternal age, and race/ethnicity to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We did not find evidence for an association between infant leukemia and eight of nine chemical categories. However, exposure to petroleum products during pregnancy was associated with AML (OR = 2.54; 95% CI:1.40-4.62) and leukemia without mixed lineage leukemia (MLL) gene rearrangements (''MLL-'') (OR = 2.69; 95% CI: 1.47-4.93). No associations were observed for exposure in the month before pregnancy. Conclusions: Gestational exposure to petroleum products was associated with infant leukemia, particularly AML, and MLL- cases. Benzene is implicated as a potential carcinogen within this exposure category, but a clear biological mechanism has yet to be elucidated.