PROJECT SUMMARY/ABSTRACT Discriminatory housing and zoning policies that cause residential racial segregation, concentrated poverty, and lack of economic opportunity often result in neighborhood disinvestment and increased neighborhood disorder. Neighborhood disorder—deterioration of the urban landscape, also known as blight—significantly impacts opioid misuse, including opioid initiation, injection drug use, opioid use disorder development and duration, and risk of opioid-involved overdose. Interventions to improve disorder have shown significant positive impacts on neighborhood crime, gun violence, and mental health. No studies have yet investigated the degree to which neighborhood disorder interventions influence opioid misuse or associated overdose risk. The broad objective of this study is to investigate the impact of community infrastructure reinvestment programs on opioid misuse and opioid overdose. In Philadelphia, government, community, and academic partnerships have resulted in structural interventions (PHS Philadelphia LandCare and Basic Systems Repair Program) to remediate vacant lots, abandoned buildings, and dilapidated homes. These programs are designed to improve neighborhood disorder in resource-deprived, minority-majority neighborhoods with little to no green space and may have distal effects on opioid misuse and associated overdose risk. Previous Philadelphia studies have shown significant reductions in crime and improved stress and depression for residents on blocks with blight remediation. This study will use spatial analysis methods and systematic social observation to address HEAL's RFA DA-23-051 Preventing Opioid Misuse and Co-Occurring Conditions by Intervening on Social Determinants. Specific aims are: (1) Investigate whether street block-level indicators of opioid misuse differ on blocks with blight remediation activities using systematic social observation methods for primary data collection of litter from opioid misuse (e.g., syringes, tourniquets) and harm reduction paraphernalia (e.g., wound care, naloxone); (2) Examine if fatal and nonfatal opioid overdose rates improved with remediation activities using a longitudinal spatial panel approach with fatal overdose data from Philadelphia's medical examiner and nonfatal overdose data from hospital emergency care visits; (3) Explore mechanisms by which remediation activities improve neighborhood indicators of opioid misuse and fatal and nonfatal overdose rates, including improved community mental health (measured by BRFSS data) and improved community social capital and social cohesion (measured by primary data collection of neighborhood structures related to these concepts), using systematic social observation and spatial analysis methods. This study will examine the impact of highly innovative place-based public health interventions on opioid misuse and fatal and nonfatal opioid overdose. Findings will provide support for expanding neighborhood disorder remediation proj...