Background: The incidence of opioid-related overdose deaths has been rising for 30 years and has been further exacerbated amidst the COVID-19 pandemic. Naloxone can reverse opioid overdose, lower death rates, and enable a transition to medication for opioid use disorder. Though current formulations for community use of naloxone have been shown to be safe and effective public health interventions, they rely on bystander presence. We sought to understand the preferences and minimum necessary conditions for wearing a device capable of sensing and reversing opioid overdose among people who regularly use opioids. Methods: We conducted a combined cross-sectional survey and semi-structured interview at a respite center, shelter, and syringe exchange drop-in program in Philadelphia, Pennsylvania, USA during the COVID-19 pandemic in August and September 2020. The primary aim was to explore the proportion of participants who would use a wearable device to detect and reverse overdose. Preferences regarding designs and functionalities were collected via a questionnaire with items having Likert-based response options and a semi-structured interview intended to elicit feedback on prototype designs. Independent variables included demographics, opioid use habits, and previous experience with overdose. Results: A total of 97 adults with an opioid-use history of at least 3 months were interviewed. A majority of survey participants (76%) reported a willingness to use a device capable of detecting an overdose and automatically administering a reversal agent upon initial survey. When reflecting on the prototype, most respondents (75.5%) reported that they would wear the device always or most of the time. Respondents indicated discreetness and comfort as important factors that increased their chance of uptake. Respondents suggested that people experiencing homelessness and those with low tolerance for opioids would be in greatest need of the device. Conclusions: The majority of people sampled with a history of opioid use in an urban setting were interested in having access to a device capable of detecting and reversing an opioid overdose. Participants emphasized privacy and comfort as the most important factors influencing their willingness to use such a device. Trial Registration: NCT04530591