Opioid overdose (OOD) is a serious public health crisis in the US. Naloxone, an opioid antagonist, reverses opioid overdoses. Data on prevalence, demographics, and healthcare utilization of OOD and OOD at-risk individuals remain largely unreported. Naloxone prescriptions for these groups are examined. This retrospective analysis used anonymized Optum health claims data, included over 180 million covered lives from Commercial, Managed Medicare and Medicaid plans. Eligible patients were ≥ 18 years old with medical and pharmacy benefits and minimum 30 days continuous enrollment from January 2016 - December 2019. ICD-10 codes for opioid poisoning were used to identify the OOD population (OODP). The OOD at-risk population (ARP) was classified utilizing one or more CDC risk factor criteria, identified through use of both ICD-10 codes and NDC drug codes. NDC drug codes were used to identify individuals prescribed naloxone in both cohorts. Of 7.87 million individuals included, prevalence of OODP declined by 9% from 2016-2019. In the same period, prevalence of ARP declined by 16%. In 2019, the largest group of OODP was aged 30-49 years (35%), male (53%), Caucasian (75%), and Medicaid beneficiaries (60%). In contrast, ARP were mostly aged ≥50 years (65%), female (61%), Caucasian (73%), and Medicare beneficiaries (70%). Only 20% of OODP and 5% of ARP received naloxone in 2019. Cost per opioid overdose episode was $3,200 for individuals on naloxone and $10,400 for those not. This large retrospective analysis suggests that despite CDC guidelines and prevalence of opioid overdose and at-risk patients, naloxone remains under-dispensed, which may result in a high healthcare utilization burden. Preliminary data suggests that previously unrecognized populations appear to be at-risk and require further evaluation. Analysis of healthcare costs associated with at-risk populations and the impact of naloxone administration on disease state management and OOD-associated morbidity and mortality is ongoing.