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The primary objective was to describe microbiologically documented infections during induction therapy for acute lymphoblastic leukemia. The secondary objectives were to describe risk factors for microbiologically documented infections and for patients with a febrile episode, to identify risk factors for recurrence of fever or reinitiation of antibiotics.This study was a retrospective review of children from 1 to 18 years of age who received induction chemotherapy between March 1997 and September 2006. Microbiologically documented infections were examined through the induction period.There were 425 children evaluated. The most common pre-existing risk factor for infection was Down syndrome in 11 children. Of the 425 children, 83 (19.5%) experienced at least one microbiologically documented infection. There were 85 infections consisting of 65 bacterial, 15 viral and 5 fungal infections.Variables significantly associated with a microbiologically documented infection were pre-existing risk factors (odds ratio [OR]: 3.63; P = 0.01) and neutropenia at initial infectious episode (OR: 1.86; P = 0.03). Factors associated with recurrence of fever and reinitiation of antibiotics after an initial infectious episode were receipt of a 4-drug induction, neutropenia at the initial infectious episode, initial fever documented in hospital, and lack of bone marrow recovery at the time of initial antibiotic cessation.About 20% of children with acute lymphoblastic leukemia have a microbiologically documented infection during induction. Those with pre-existing risk factors and neutropenia at the initial infectious episode were at higher risk of microbiologically documented infection. Continued efforts to refine risk groups may allow for risk-directed prophylactic or empiric strategies.