We propose to conduct a randomized controlled trial to test the effectiveness and cost -effectiveness of an intervention designed to increase and improve equitable naloxone distribution in 48 syringe service programs (SSPs) throughout California. In the past 5 years, opioid overdose mortality rates increased 114% among Black, 97% among Latinx, and 32% among White populations. Opioid overdose fatalities are preventable with the timely administration of naloxone, an opioid antagonist, yet our research has shown that Black and Latinx people who inject drugs (PWID) are 25% and 47% less likely, respectively, to receive naloxone than White PWID. Building on pilot work (R21DA046703; Principal Investigator: Lambdin), we will use the Systems Analysis and Improvement Approach to improve equitable access to naloxone from SSPs (SAIA-Naloxone). In our pilot study with two SSPs in California, we found that SAIA-Naloxone led to an average increase of 23 more people receiving naloxone (p<0.001) and 64 more naloxone doses bein g distributed (p<0.001) per week. We observed a 116% increase in naloxone distribution to participants who were Black, Indigenous, or People of Color (BIPOC). SAIA-Naloxone was feasible and acceptable, and it resulted in meaningful improvements in naloxone penetration. We are now proposing to test SAIA-Naloxone in a large-scale randomized controlled trial. To effectively address opioid overdoses, SSP-based naloxone programs must engage participants in a series of sequential steps including screening participants; training them in naloxone administration; distributing naloxone; and building systems that support participants to possess naloxone, use naloxone during overdose events, and obtain naloxone refills as needed. This paradigm is known as the naloxone delivery cascade. SAIA-Naloxone is a multicomponent implementation strategy designed to help SSPs identify and address weaknesses along the naloxone delivery cascade. It includes determination of drop-offs in cascade delivery, process mapping and consensus discussions to identify potential solutions, and continuous quality improvement. Our Aim 1 is to test the effectiveness of SAIA-Naloxone on improving naloxone distribution at SSPs, relative to treatment as usual. Aim 2 is to test the effectiveness of SAIA-Naloxone on improving naloxone distribution at SSPs to BIPOC participants, relative to treatment as usual. Aim 3 is to estimate the cost and cost-effectiveness of SAIA-Naloxone on improving equitable access to naloxone at syringe service programs, relative to treatment as usual. This project will directly contribute to the improvement of minority health and the reduction of health disparities. The proposed study aligns with the goals of the Department of Health and Human Services and the Substance Abuse and Mental Health Services Administration, which recognize naloxone access as our nation’s first defense to prevent opioid overdose deaths.