OBJECTIVE: Take-home naloxone (THN) reduces deaths from opioid overdose. To increase THN distribution to at-risk emergency department (ED) patients, we explored reasons for patients' refusing or accepting THN. METHODS: In an urban teaching hospital ED, we identified high opioid overdose risk patients according to pre-specified criteria. We offered eligible patients THN and participation in researcher-administered surveys, which inquired about reasons to refuse or accept THN and about THN dispensing location preferences. We analyzed refusal and acceptance reasons in open-ended responses, grouped reasons into categories (absolute versus conditional refusals,) then searched for associations between patient characteristics and reasons. RESULTS: Of 247 patients offered THN, 193 (78.1%) provided reasons for their decision. Of those included, 69 (35.2%) were female, 91 (47.2%) were under age 40, 61 (31.6%) were homeless, 144 (74.6%) reported injection drug use (IDU), and 131 (67.9%) accepted THN. Of 62 patients refusing THN, 19 (30.7%) felt "not at risk" for overdose, while 28 (45.2%) gave conditional refusal reasons: "too sick," "in a rush," or preference to get THN elsewhere. Non-IDU was associated with stating "not at risk," while IDU, homelessness, and age under 40 were associated with conditional refusals. Among acceptances, 86 (65.7%) mentioned saving others as a reason. Most respondents preferred other dispensing locations beside the ED, whether or not they accepted ED THN. CONCLUSION: ED patients refusing THN felt "not at risk" for overdose or felt their ED visit was not the right time or place for THN. Most accepting THN wanted to save others.