OBJECTIVES Myelosuppressive chemotherapy can lead to neutropenia and increase infection risk. Myeloid growth factors are commonly used to treat/prevent neutropenia. Sargramostim is a granulocyte-macrophage colony-stimulating factor (GM-CSF). Unlike filgrastim and pegfilgrastim, which are granulocyte colony-stimulating factors (G-CSFs), sargramostim activates a broader range of myeloid lineage-derived cells. Therefore, GM-CSF might reduce infection risk more than G-CSFs. This study compared real-world infection-related hospitalization rates and costs in patients using G/GM-CSF for chemotherapy-induced neutropenia. METHODS This retrospective matched-cohort study analyzed nationally-representative health insurance claims in the US in 2000-2007. The sample population included patients who received chemotherapy and G/GM-CSF. G/GM-CSF treatment episodes began with the first administration of G/GM-CSF and ended when a subsequent administration was >28 days after a prior administration. Sargramostim patients were matched 1:1 with filgrastim and pegfilgrastim patients based on gender and birth year. Outcomes included infection-related hospitalization rates and the associated costs. Hospitalization rates were analyzed using univariate and multivariate Poisson methods; covariates included myelosuppressive agents received, tumor type, anemia, and comorbidities. RESULTS A total of 990 sargramostim-filgrastim and 982 sargramostim-pegfilgrastim pairs were analyzed. Cohorts had similar baseline characteristics, though differences were observed in the fraction of patients with a neutropenia diagnosis (sargramostim 65%, filgrastim 57%, pegfilgrastim 45%) and who received myelosuppressive agents (sargramostim 54%, filgrastim 48%, pegfilgrastim 77%). Sargramostim patients experienced infection-related hospitalizations about half as often as filgrastim (p=0.04) or pegfilgrastim (p=0.06) patients. Multivariate analyses adjusted for confounding factors and found that sargramostim patients were 56% less likely to have infection-related hospitalizations compared to filgrastim and pegfilgrastim patients (p=0.03 for both). Infection-related hospitalization costs for sargramostim patients were $728/patient/month and $226/patient/month less compared to filgrastim (p=0.04) and pegfilgrastim patients (p=0.01), respectively. CONCLUSIONS Among patients with chemotherapy-induced neutropenia, sargramostim use is associated with reduced risk of infection-related hospitalization and lower associated costs compared to filgrastim or pegfilgrastim.