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Purpose Estimate the total costs to society of prescription opioid analgesic (RxO) abuse in the United States in 2001. Methods For this analysis, “drug abuse” refers to any nonmedical use of a drug, including that which meets the DSM-IV criteria for substance abuse or dependence disorders. The costs associated with RxO abuse were grouped into three major cost categories: health care, lost productivity, and criminal justice. Each category has multiple underlying components. Relying primarily on published data, we used varying methods, depending on the cost component considered. In general, cost estimates were obtained by either (i) a quantity method, which multiplies the relevant number of RxO abusers based on various national surveys (e.g., National Household Survey on Drug Abuse, Treatment Admissions Data Set, Drug Abuse Warning Network) by the per abuser cost, or (ii) an apportionment method, which starts with the overall costs of drug abuse for a particular cost component (e.g., prevention programs) and apportions the share solely due to RxO abuse based on the prevalence of RxO abuse relative to overall (i.e., licit plus illicit) drug abuse. An additional data source (for excess medical costs) was an administrative claim database for an employed population of approximately 600,000 lives. Results Total costs of RxO abuse in the United States in 2001 were $9.2 billion. Of these costs, $2.8 billion were health care costs, $4.6 billion were lost productivity costs, and $1.8 billion were criminal justice costs. These estimates are lower-bound estimates, in that some cost categories and components—such as diversion—were not included. Sensitivity analyses found that costs for the estimated cost categories and components could range up to $11.5 billion. Conclusion The costs of RxO abuse in the United States impose a substantial economic burden to society. Rising trends of prescription opioid abuse suggest an escalating economic and public health burden in coming years.