Project Summary The quantity of opioid prescriptions dispensed in the United States (US) is so high that every other person could receive one opioid prescription. Many of these opioids go unused and are kept in homes rather than disposed after ceasing use. The primary source of prescription opioids for nonmedical use is relatives or friends; which suggests that diversion of excess and retained prescription opioids contribute significantly to nonmedical use and associated consequences. Without effective strategies to facilitate their secure storage and disposal, prescription opioids will remain in communities, increasing the likelihood for nonmedical use- related morbidity and mortality. Our long-term goal is to prevent nonmedical prescription opioid use by decreasing accessibility of unused medications in the home. The overall objective of this R03 application is to assess (1) the extent to which disposal boxes have been implemented in pharmacies across the US, (2) accessibility of disposal boxes to diverse community members, and (3) determinants of implementation. To achieve this objective, we propose two specific aims: (1) generate prevalence estimates of disposal box implementation in US pharmacies and examine place-based health disparities in implementation, and (2) examine determinants of pharmacy-based disposal box implementation using the Consolidated Framework for Implementation Research (CFIR). For Aim 1, we will sample 1,000 of the nation's approximately 60,000 retail pharmacies, geocode locations, and link with disposal box presence and neighborhood characteristics. We will conduct logistic regression with clustering to examine inequities in neighborhood characteristics that are associated with disposal box implementation (primary outcome). For Aim 2, we will conduct semi-structured interviews with a sample of 60 pharmacies who have and have not implemented medicine disposal boxes and will link geocoded neighborhood characteristics with qualitative data. The proposed research study is innovative, in our opinion, in that it applies an approach that has been piloted by the PI in a single state to study pharmacy-based disposal boxes by (1) developing nationwide prevalence estimates of disposal boxes across the US, (2) examining place-based health disparities associated with implementation, (3) assessing determinants of implementation using a theoretical framework, and (4) uniquely linking interview themes and neighborhood characteristics. The proposed research is significant in that findings will advance the understanding of inequities in and determinants of disposal box implementation at pharmacies and pave the way for comparative efficacy studies. The proposed study is relevant to NIDA's priorities to implement and evaluate theoretically-based, prevention interventions that can be implemented in healthcare settings to elicit population-level impacts to address the ongoing opioid crisis.