AbstractPurposeSince 1990, numerous jurisdictions in the United States (US) have reported increases in drug poisoning mortality. During the same time period, the use of opioid analgesics has increased markedly as part of more aggressive pain management. This study documented a dramatic increase in poisoning mortality rates and compared it to sales of opioid analgesics nationwide.MethodsTrend analysis of drug poisoning deaths using underlying cause of death and multiple cause of death mortality data from the Centers for Disease Control and Prevention and opioid analgesic sales data from the US Drug Enforcement Administration.ResultsUnintentional drug poisoning mortality rates increased on average 5.3% per year from 1979 to 1990 and 18.1% per year from 1990 to 2002. The rapid increase during the 1990s reflects the rising number of deaths attributed to narcotics and unspecified drugs. Between 1999 and 2002, the number of opioid analgesic poisonings on death certificates increased 91.2%, while heroin and cocaine poisonings increased 12.4% and 22.8%, respectively. By 2002, opioid analgesic poisoning was listed in 5528 deaths—more than either heroin or cocaine. The increase in deaths generally matched the increase in sales for each type of opioid. The increase in deaths involving methadone tracked the increase in methadone used as an analgesic rather than methadone used in narcotics treatment programs.ConclusionsA national epidemic of drug poisoning deaths began in the 1990s. Prescriptions for opioid analgesics also increased in this time frame and may have inadvertently contributed to the increases in drug poisoning deaths. Copyright © 2006 John Wiley & Sons, Ltd.