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This study estimates the costs to society of prescription opioid analgesic (RxO) abuse in the United States.Costs associated with RxO abuse were grouped into healthcare, criminal justice, and workplace categories. Costs were estimated by either (1) a quantity method that multiplies the number of RxO abusers derived from various national surveys by the estimated per abuser cost, or (2) an apportionment method that starts with overall (ie, prescription and nonprescription) drug abuse costs for a cost component (eg, police protection) and apportions the share of costs based on the prevalence of RxO abuse relative to overall drug abuse. Medical costs in excess of those for otherwise similar nonabusers were based on an analysis of a large administrative claims database for an employed population using multivariate regression methods.A lower bound estimate of the costs of RxO abuse in the United States was $8.6 billion in 2001 (or $9.5 billion in 2005 dollars). Of this amount, $2.6 billion were healthcare costs, $1.4 billion were criminal justice costs, and $4.6 billion were workplace costs.The costs of RxO abuse represent a substantial economic burden. Rising trends of RxO abuse suggest an escalating economic and public health burden in coming years in the United States, and potentially, elsewhere.