Abstract Context Antibiotic prescription in hospice patients is complicated by the focus on palliative rather than curative care and concerns regarding increasing antibiotic resistance. Objectives To estimate the antibiotic use in a national sample of hospice patients and identify facility and patient characteristics associated with antibiotic use in this population. Methods This was an analysis of data from the 2007 National Home and Hospice Care Survey, a nationally representative sample of U.S. hospice agencies. We included data from 3884 patients who died in hospice care. The primary outcome measure was prevalence of antibiotic use in the last seven days of life. Diagnoses, including potential infectious indications for antibiotic use, were defined using International Classification of Diseases, Ninth Revision (ICD-9) codes. Chi-squared tests and t -tests were used to quantify associations of patient and facility characteristics with antibiotic use. Results During the last seven days of life, 27% (95% CI: 24%–30%) of patients received at least one antibiotic and 1.3% (95% CI: 0.7%–2.0%) received three or more antibiotics. Among patients who received at least one antibiotic, 15% (95% CI: 10%–20%) had a documented infectious diagnosis compared with 9% (95% CI: 7%–11%), who had an infectious diagnosis but received no antibiotics. Conclusion In this nationally representative sample, 27% of hospice patients received an antibiotic during the last seven days of life, most without a documented infectious diagnosis. Further research is needed to elucidate the role of antibiotics in this patient population to maintain palliative care goals while reducing unnecessary antibiotic use.