The MS Department of Mental Health, with the MS Public Health Institute, MS Center for Emergency Services, and Bartkowski & Associates Research Team, proposes ARIES-PDO (hereafter ARIES), MS’s Active Response Implementation and Evaluation System for prescription drug/opioid overdose prevention. ARIES will train and educate at least 7000 persons (first responders, healthcare workers, other staff, and residents) in naloxone knowledge and skills, focusing primarily on a designated high-need geographical area. ARIES will also implement an aggressive naloxone distribution and utilization tracking program. MS leads the nation in negative social indicators (e.g., poverty, health disparities, medical underservice), and has unusually high overdose and overdose fatality rates due largely to the availability and abundance of high-potency opioids within the state. ARIES’s goals are these: Goal 1: Improve the naloxone education and distribution process over the course of five project years, to include a one tenth (Obj. 1.1) reduction in the rate of intentional, unintentional, and undetermined intentional opioid overdose; (Obj. 1.2) reduction in the number of opioid overdose-related deaths; (Obj. 1.3) increase in the number of opioid overdose reversals; (Obj. 1.4) increase in the number of referrals to substance abuse treatment services; (Obj. 1.5) increase in the number of individuals receiving treatment or recovery services following successful overdose reversal administration; and (Obj. 1.6) increase in the number of naloxone kits that reached high-need communities. Goal 2: Enhance education and training programs for 7000 individuals, meeting or exceeding projected annual numbers of (Obj. 2.1) trainings conducted on opioid overdose death prevention strategies; (Obj. 2.2) medical professionals trained on overprescribing risks; (Obj. 2.3) first responders trained on using overdose reversal drugs; (Obj. 2.4) participants per session by type of participant; people reporting (Obj. 2.5) learning, (Obj. 2.6) using, and (Obj. 2.7) having confidence in training knowledge/skills; (Obj. 2.8) individuals accurately recognizing overdose symptoms; and (Obj. 2.9) improved rates of successful administration of overdose-reversing drugs tracked in real time. Goal 3: Improve naloxone utilization, to include a one tenth increase in the (Obj. 3.1) number of naloxone kits used in each administration and by type of kit; (Obj. 3.2) total amount and percentage of funds spent to purchase naloxone products; (Obj. 3.3) number of referrals to kit prescriber or other medical professional post-administration for replacement resources, etc.; (Obj. 3.4) number of persons administering naloxone by type, disparity demographics, number of prior administrations, and census tract; (Obj. 3.5) number of naloxone patients by location of administration, disparity demographics, number of prior administrations, and census tract; and (Obj. 3.6) number of naloxone kits distributed by zip code, request vs. response, household, dosage amount, type of recipient, and type of kit.