More than one million people have died from accidental drug overdose in the United States (US) in the past 20 years. In response to this unabating crisis, New York City opened the first two publicly recognized overdose prevention centers (OPCs) in the nation in November 2021. Rhode Island became the first state to authorize OPCs through state legislation, with the third US OPC opening in January 2025. OPCs are fixed-site facilities where individuals may consume pre-obtained controlled substances under the supervision of trained personnel who can intervene in the event of an overdose. Staff at OPCs also provide overdose prevention and response education, offer health and ancillary services, and provide referrals to other treatment, health, and recovery services. While research from other countries suggest that OPCs produce individual health and community benefits, no evaluations exist of publicly recognized OPCs in the US. The proposed study will evaluate the public health, public safety, and community impacts—and potential unintended effects—of the first publicly recognized OPCs in the US. We propose to conduct a rigorous, multi-site, multi-component evaluation of OPCs in New York City and Rhode Island in 2023-2027. At the individual level, we aim to evaluate whether a prospective cohort of 500 persons attending OPCs experience lower rates of overdose, other health problems, and emergency department use, and a higher rate of substance use disorder treatment initiation, compared to a cohort of 500 persons who do not attend OPCs (Aim 1). At the community level, we will examine whether neighborhoods surrounding the OPCs experience a greater change in overdoses, measures of public disorder, and acute economic conditions following the opening of OPCs, compared to neighborhoods unexposed to OPCs (Aim 2). Third, we aim to examine how operational factors, including location, program model, and procedures, affect OPC performance (Aim 3). Finally, we will estimate additional