OBJECTIVE—To use bone marrow transplantation (BMT) as a model for testing the association between hyperglycemia and infection. RESEARCH DESIGN AND METHODS—This cohort study included 382 adults (6.5% with diabetes) who had no evidence of infection before neutropenia during BMT. Mean glucose was calculated from central laboratory and bedside measurements taken before neutropenia; the primary outcome was neutropenic infections. RESULTS—Eighty-four patients (22%) developed at least one neutropenic infection, including 51 patients (13%) with bloodstream infections. In patients who did not receive glucocorticoids during neutropenia, each 10 mg/dl increase in mean preneutropenia glucose was associated with an odds ratio of 1.08 (95% CI 0.98–1.19) (P = 0.14) for any infection and 1.15 (1.03–1.28) (P = 0.01) for bloodstream infections, after adjusting for age, sex, race, year, cancer diagnosis, transplant type, and total glucocorticoid dose before neutropenia. In those who received glucocorticoids during neutropenia (n = 71), the adjusted odds ratio associated with a 10 mg/dl increase in mean glucose was 1.21 (1.09–1.34) (P < 0.0001) for any infection and 1.24 (1.11–1.38) (P < 0.0001) for bloodstream infections. There was no association between mean glycemia and long length of hospital stay, critical status designation, or mortality. CONCLUSIONS—In a BMT population highly susceptible to infection, there was a continuous positive association between mean antecedent glycemia and later infection risk, particularly in patients who received glucocorticoids while neutropenic. Tight glycemic control during BMT and glucocorticoid treatment may reduce infections.