BACKGROUND The decision to utilize antimicrobials in end-of-life situations is complex. Understanding the reasons why physicians prescribe antimicrobials in this patient population is important for informing the design of antimicrobial stewardship interventions. METHODS A 51-item survey containing both closed and open-ended questions on end-of-life antimicrobial use was administered to physicians affiliated with the University of Pennsylvania and Children’s Hospital of Philadelphia from January through April 2017. A mixed-methods approach was used to analyze responses. RESULTS Of 637 physicians surveyed, 283 responses (44.4%) were received. Most (86.2%) physicians believed that respecting a patient’s wish to continue antimicrobials was important. Approximately half of physicians (49.8%) believed that antimicrobial use at the end of life contributes to resistance. A higher proportion of pediatricians would often or always continue antimicrobial treatment for active infections and for hospice patients whose death was imminent compared to adult physicians (P<.001). Analysis of free-text responses revealed additional reasons why physicians may continue antimicrobials at end of life, including meeting family expectations, wanting to avoid the perception of "giving up," uncertainty about prognosis, and reducing patient pain or discomfort. CONCLUSIONS Physician decision making concerning antimicrobial use in patients at the end of life is multifactorial. Clinicians may overweigh the benefits of antimicrobial therapy in end-of-life situations and view the importance of adhering to stewardship policies differently. Pediatric and adult clinicians have different approaches to this patient population. Better understanding of the complex decision making that occurs in the end-of-life patient population can help guide antimicrobial stewardship policies and improve patient care. Infect Control Hosp Epidemiol 2018;39:383-390.