OBJECTIVES: The purpose of this study was to estimate the effect of clinical and demographic patient characteristics, and insurance status on hospital charges associated with opioid abuse or misuse in the United States. METHODS: Data for this study were derived from the 2006, 2007, and 2008 Healthcare Cost and Utilization Project’s Nationwide Emergency Departments Sample (HCUP-NEDS). Events and charges related to opioid abuse, dependence, or poisoning overall and by insurance status (Medicaid, Medicare, private insurance, or self-pay) were estimated using ICD-9-CM codes 304.0X, 304.7X, 305.5X, 965.00, 965.02, and 965.09, accounting for the complex sampling of the HCUP-NEDS. Charges were adjusted using the 2010 Medical Consumer Price Hospital Services index. RESULTS: Total charges were $9.8; $9.6; and $9.5 billion for 2006, 2007, and 2008, respectively. The highest total charges were associated with events for which Medicaid was the expected primary payer (~$3.3 billion), followed by Medicare (~$2.2 billion) for each year In 2006, charges were $2.0 billion for self-paid events, and $1.7 billion for privately insured events; this relationship was reversed in 2007 and 2008. Adjusted mean per-event charges were $19,413; $19,560; and $17,690 for 2006, 2007, and 2008, respectively. Compared to events covered by private insurance, adjusted charges for Medicare- and Medicaid-covered events were statistically significantly higher, while self-paid events had significantly lower charges (p <0.001 for all years). Age, number of comorbidities, presence of cardiac or respiratory disease, gastrointestinal hemorrhage, and acute pancreatitis were significantly positively associated with total charges (p <0.001 for all). CONCLUSIONS: The economic burden of opioid abuse on the healthcare system is substantial and associated charges are related to insurance status. Factors associated with charges for events related to opioid abuse or misuse were also identified, resulting in better understanding of costs of opioid abuse and misuse.