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Purpose: We retrospectively compared the outcomes and costs of outpatient and inpatient management of low-risk outpatients who presented to an emergency department with febrile neutropenia (FN)., Patients and Methods: A single episode of FN was randomly chosen from each of 712 consecutive, low-risk solid tumor outpatients who had been treated prospectively on a clinical pathway (1997-2003). Their medical records were reviewed retrospectively for overall success (resolution of all signs and symptoms of infection without modification of antibiotics, major medical complications, or intensive care unit admission) and nine secondary outcomes. Outcomes were assessed by physician investigators who were blinded to management strategy. Outcomes and costs (payer's perspective) in 529 low-risk outpatients were compared with 123 low-risk patients who were psychosocially ineligible for outpatient management (no access to caregiver, telephone, or transportation; residence > 30 minutes from treating center; poor compliance with previous outpatient therapy) using univariate statistical tests., Results: Overall success was 80% among low-risk outpatients and 79% among low-risk inpatients. Response to initial antibiotics was 81% among outpatients and 80% among inpatients (P = .94); 21% of those initially treated as outpatients subsequently required hospitalization. All patients ultimately responded to antibiotics; there were no deaths. Serious complications were rare (1%) and equally frequent between the groups. The mean cost of therapy among inpatients was double that of outpatients ($15,231 v $7,772; P < .001)., Conclusion: Outpatient management of low-risk patients with FN is as safe and effective as inpatient management of low-risk patients and is significantly less costly.